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Sample records for intrathecal long-acting liposomal

  1. Neurologic complications after intrathecal liposomal cytarabine in combination with systemic polychemotherapy in primary CNS lymphoma.

    PubMed

    Ostermann, Kathrin; Pels, Hendrik; Kowoll, Annika; Kuhnhenn, Jan; Schlegel, Uwe

    2011-07-01

    Intrathecal application of liposomal cytarabine (Ara-C) (DepoCyte(®)) has been associated with neurotoxicity when applied as part of a polychemotherapy regimen. Patients with primary central nervous system lymphoma treated with high-dose systemic methotrexate (MTX)- and Ara-C-based polychemotherapy including six cycles of liposomal Ara-C (50 mg intrathecally every 3 weeks) were prospectively monitored for neurotoxic side-effects. Between November 2005 and February 2009, 149 intrathecal applications of liposomal cytarabine (DepoCyte(®)) were carried out in 33 patients, 7 (21%) of whom developed an incomplete conus medullaris/cauda equina syndrome with incontinence for bladder (6) and bowel function (3) or lumbosacral polyradicular paresis (1), resolving only incompletely over a follow-up period of 9-30 months. In six of these seven patients, lumbosacral magnetic resonance imaging (MRI) was negative for leptomeningeal infiltration or arachnoiditis. Cerebrospinal fluid (CSF) analysis performed in six of these seven patients showed normal cell count in all and increased total protein in four of them. One patient among these seven suffered a seizure without other identifiable causes. Conus/cauda syndrome has to be considered as a serious potential neurotoxic side-effect in patients receiving liposomal Ara-C as part of a multimodal regimen including high-dose systemic MTX and Ara-C. PMID:20953896

  2. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

    PubMed Central

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-01-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m2 in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3–4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). PMID:25749825

  3. Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study.

    PubMed

    Benesch, Martin; Siegler, Nele; Hoff, Katja von; Lassay, Lisa; Kropshofer, Gabriele; Müller, Hermann; Sommer, Constanze; Rutkowski, Stefan; Fleischhack, Gudrun; Urban, Christian

    2009-10-01

    This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors. Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1). Eighteen patients received concomitant systemic radiochemotherapy. A total of 88 intrathecal injections of liposomal cytarabine (dose range, 20-50 mg) were administered with concomitant dexamethasone prophylaxis. The median number of doses per patient was four (range, 1-10). Duration of treatment ranged from (1/2) to 10 months. Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2). Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients. Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects. In conclusion, although intrathecal liposomal cytarabine was generally well tolerated, it should be used cautiously and only with dexamethasone prophylaxis in extensively pretreated patients with recurrent brain tumors. Proof of efficacy requires a prospective single-agent phase II study. PMID:19617818

  4. Efficacy and safety of intrathecal liposomal cytarabine for the treatment of meningeal relapse in acute lymphoblastic leukemia: experience of two pediatric institutions.

    PubMed

    Parasole, Rosanna; Menna, Giuseppe; Marra, Nicoletta; Petruzziello, Fara; Locatelli, Franco; Mangione, Argia; Misuraca, Aldo; Buffardi, Salvatore; Di Cesare-Merlone, Alessandra; Poggi, Vincenzo

    2008-08-01

    The treatment of meningeal relapse in acute lymphoblastic leukemia (ALL) remains a challenging clinical problem. Liposomal cytarabine (DepoCyte) permits to decrease frequency of lumbar punctures, without loss of efficacy, because intrathecal levels of the drug remain cytotoxic for up to 14 days. We investigated the efficacy and safety of intrathecal DepoCyte in six children with meningeal relapse, treated in two pediatric institutions. DepoCyte was well tolerated in all patients, who achieved complete clearance of blasts from the cerebrospinal fluid after the first three intrathecal drug administrations. Five of the six patients were concurrently treated with high-dose administration of systemic cytarabine, without additional neurological side effects. Our results suggest that DepoCyte is a valid option for children with ALL experiencing meningeal relapse; it deserves further investigation in intensive treatment regimens, taking into due consideration potential neurotoxicity. PMID:18766969

  5. Compassionate use of intrathecal depot liposomal cytarabine as treatment of central nervous system involvement in acute leukemia: report of 6 cases.

    PubMed

    Sancho, Juan-Manuel; Ribera, Josep-Maria; Romero, Maria-José; Martín-Reina, Victoria; Giraldo, Pilar; Ruiz, Elena

    2006-03-01

    The depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful as intrathecal (IT) treatment of neoplastic and lymphomatous meningitis. We report the results of compassionate use of DepoCyte in 6 patients diagnosed with acute leukemia (AL) and CNS involvement. Two patients had CNS involvement at diagnosis and the remaining 4 had CNS relapse. Three patients received DepoCyte as adjuvant therapy and achieved complete response whereas 2 out of the remaining 3 cases treated with DepoCyte as the only drug showed sustained response. The side effects were mild and manageable in all patients. These findings justify the development of clinical trials to evaluate the efficacy and safety of IT depot cytarabine in meningeal involvement of AL. PMID:16533729

  6. Liposomes.

    PubMed

    Posner, Robert

    2002-09-01

    Robert Posner has 40 years of experience in skin care bench chemistry, product development, and sales and marketing. Working closely with dermatologists and plastic surgeons, Posner is a former member of the NY State Hospital Pharmacists Association, the American Pharmaceutical Association, and the American Association of Hospital Pharmacists. Currently, Posner sits on the Board of Directors of EMDA (Esthetic Manufacturers and Distributors Association). Posner has written numerous articles for Les Nouvelles Esthetiques Magazine, is presently a consultant for Day Spa Magazine, and had been one of only two non-dermatologists on a consultant basis with Cosmetic Dermatology Journal. Posner's company--ABBE Cosmetic Group International in Farmingdale, NY--formulates and manufactures skin care products for many well-known companies in the beauty industry. For many years, both the bench chemist and the dermatologist have been concerned with developing an ideal base for deliverance of 'actives' to the human epidermis. As is common knowledge, the skin is a protective organ which allows very few materials to penetrate. Some bases are unable to work effectively because of their relative inability to penetrate the stratum corneum; for example, some notable actives such as collagen and elastin are molecules too large to penetrate effectively. With the liposome at our command however, we can carry and then release an active into several layers of epidermis. We can release both oil- and water-soluble actives, and at the same time control the feel and effectiveness of a topical application. This article will examine the liposome: what it is, how it works, and how products made with liposomes can benefit dermatology. PMID:12847740

  7. Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

    PubMed

    González-Barca, E; Canales, M; Salar, A; Ferreiro-Martínez, J J; Ferrer-Bordes, S; García-Marco, J A; Sánchez-Blanco, J J; García-Frade, J; Peñalver, J; Bello-López, J L; Sancho, J M; Caballero, D

    2016-05-01

    The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL. PMID:27025508

  8. Long-acting muscarinic antagonists.

    PubMed

    Melani, Andrea S

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients. PMID:26109098

  9. Long-acting hormonal contraception.

    PubMed

    Benagiano, Giuseppe; Gabelnick, Henry; Brosens, Ivo

    2015-11-01

    Today, a new category of fertility-regulating agents has been created: long-acting, reversible hormonal contraceptives; they minimize compliance, while maximize effectiveness. They comprise subdermal implants and intrauterine devices. Other long-acting agents exist, such as Depo Provera and Noristerat. Use of Depo Provera and Noristerat carries great effectiveness, good clinical safety and usefulness in developing countries. They cause no significant increase in breast cancer risk, but they may carry an increased risk of HIV. Subcutaneous delivery systems have two common features: prolongation of effect is obtained by a drug reservoir and for most of their duration of action they provide a continuous, sustained release of the active hormone. Finally, the intrauterine system Mirena represents both a very effective contraceptive and a specific treatment for menorrhagia. PMID:26626534

  10. Long-acting contraceptive options.

    PubMed

    Kaunitz, A M

    1996-01-01

    Long-acting contraceptive methods are appropriate choices for women who prefer the convenience and high contraceptive efficacy of methods not requiring frequent compliance, and women for whom contraceptive doses of estrogen are either medically contraindicated or associated with persistent intolerable side effects. Annual pregnancy rates for the three methods described below are less than 1 per 100 woman-years. As currently formulated, levonorgestrel implants (Norplant) consist of six 34 x 2.4 mm soft plastic implants, each filled with 36 mg of crystalline levonorgestrel. Irregular and often persistent menstrual bleeding and spotting constitute the most important side effects experienced by and leading to method discontinuation in implant users. Implant removal is technically more difficult and time-consuming than insertion. Depot-medroxyprogesterone acetate (DMPA or Depo-Provera) is injected as an aqueous suspension of microcrystals. Intramuscular injection of 150 mg of DMPA results in more than 3 months of contraception. Irregular bleeding and spotting followed by amenorrhea, constitute the most importance side effects experienced by DMPA users. Because DMPA use can result in prolonged (but not permanent) infertility, DMPA is not an optimum contraceptive choice for women who may want to conceive in the next one or two years. The Copper T380A intrauterine device (IUD) provides reversible contraception for up to 10 years. IUDs act as contraceptives, not early abortafacients. Recent epidemiologic data indicate that long-term IUD use does not increase the occurrence of pelvic inflammatory disease. Heavier menstrual flow and cramps constitute the main side effects experienced by women using the copper IUD. Intrauterine device insertion and removal are accomplished during brief office-based procedures. PMID:8829701

  11. Long-acting local anesthetics in dentistry.

    PubMed Central

    Sisk, A. L.

    1992-01-01

    Long-acting local anesthetics have proved to be effective for the suppression of both intraoperative and postoperative pain. They are useful for lengthy dental treatments and for prevention of severe pain following many types of surgical procedures. Although the currently available long-acting local anesthetics for dentistry have minimal side effects in the doses usually employed, there are potential problems. Bupivacaine, for example, can cause significant cardiac depressant and dysrhythmogenic responses. Etidocaine has less pronounced effects on the cardiovascular system, but its use may be associated with inadequate control of intraoperative bleeding. A new long-acting local anesthetic, ropivacaine, appears to offer advantages over either of the currently used long-acting agents. PMID:1308373

  12. Long-acting preparations of exenatide

    PubMed Central

    Cai, Yunpeng; Wei, Liangming; Ma, Liuqing; Huang, Xiwen; Tao, Anqi; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Exenatide has been widely used for the treatment of type 2 diabetes mellitus. However, its short plasma half-life of 2.4 hours has limited its clinical application. The exenatide products on the market, twice-daily Byetta™ and once-weekly Bydureon™ (both Amylin Pharmaceuticals, San Diego, CA, USA), are still not perfect. Many researchers have attempted to prolong the acting time of exenatide by preparing sustained-release dosage forms, modifying its structure, gene therapies, and other means. This review summarizes recent advances in long-acting exenatide preparations. PMID:24039406

  13. Femoral Nerve Block Versus Long-Acting Wound Infiltration in Total Knee Arthroplasty.

    PubMed

    Emerson, Roger H; Barrington, John W; Olugbode, Oluseun; Lovald, Scott; Watson, Heather; Ong, Kevin

    2016-05-01

    Multimodal wound infiltration analgesic techniques have attracted growing interest for applications in total knee arthroplasty (TKA). A benefit of using wound infiltration instead of femoral nerve block (FNB) in a multimodal pain control regimen is the limitation of muscle strength impairment to the surgical area, which will focus the pain control effort and may provide the opportunity for easier rehabilitation and earlier discharge from the hospital. The current study directly compares patients undergoing TKA who are given a continuous FNB with those who were administered an injection of liposomal bupivacaine infiltration. The study cohort included 36 patients with osteoarthritis who were treated with a continuous FNB (OnQ pump; I-Flow, Lake Forest, California), and 36 patients who were administered an injection for liposome bupivacaine infiltration (EXPAREL; Pacira Pharmaceuticals, Inc, Parsippany, New Jersey) for postoperative pain analgesia. The average number of narcotic doses and the total number of narcotics consumed was greater in the FNB group (P<.001). Average visual analog scale pain scores trended higher for patients in the FNB group (2.29 vs 1.93) overall and for each day postoperatively up to day 5, although the overall difference was not significant in this study sample (P=.115). The results of the current study support the conclusion that long-acting liposome bupivacaine infiltration gives comparable postoperative analgesia compared with a continuous FNB, but with significantly less narcotic medication. [Orthopedics. 2016; 39(3):e449-e455.]. PMID:27018607

  14. Lumbar reservoir for intrathecal chemotherapy.

    PubMed

    Dyck, P

    1985-06-15

    The Ommaya ventricular reservoir has been the standby of intrathecal chemotherapy for more than a decade, in spite of some specific drawbacks. A general anaesthetic is often required. The scalp must be shaven. Ventricular puncture may not always be easy and keeping the ventricular catheter patent is sometimes difficult. Hence the author has adapted a commercially available lumbar peritoneal shunt system to function as a lumbar intrathecal reservoir. The procedure is simple and can be performed expeditiously under local anaesthesia. To date, eight cases have received intrathecal chemotherapy by this means. PMID:3838918

  15. [Aripiprazole long-acting for the maintenance treatment of schizophrenia.

    PubMed

    Samalin, L; Charpeaud, T; Llorca, P-M

    2014-11-13

    Antipsychotics are the cornerstone for the maintenance treatment of schizophrenia patients. Their long-acting formulations are helpful for preventing relapses through improvement of adherence to medication and a better pharmacokinetic coverage. However, their use is often reserved for refractory or non-observant clinical forms because of limitations among both clinicians and patients. The development of a new formulation of long-acting injectable aripiprazole administered every 4 weeks is a new option. Two randomized controlled trials vs. placebo and vs. oral aripiprazole respectively show a superiority and non-inferiority in terms of relapse prevention. Meanwhile, a mirror-image study demonstrates fewer hospitalizations. The safety profile is comparable to the oral formulation, particularly in terms of metabolic and neurological side-effects. As mentioned in various professional recommendations, long-acting injectable antipsychotics, so long-acting injectable aripiprazole, are one of the major strategies of the maintenance treatment for patients with schizophrenia. PMID:25453734

  16. Intrathecal delivery of analgesics.

    PubMed

    De Andres, Jose; Asensio-Samper, Juan Marcos; Fabregat-Cid, Gustavo

    2014-01-01

    Targeted intrathecal (IT) drug delivery systems (IDDS) are an option in algorithms for the treatment of patients with moderate to severe chronic refractory pain when more conservative options fail. This therapy is well established and supported by several publications. It has shown efficacy and is an important tool for the treatment of spasticity, and both cancer and nonmalignant pain. Recent technological advances, new therapeutic applications, reported complications, and the costs as well as maintenance required for this therapy require the need to stay up-to-date about new recommendations that may improve outcomes. This chapter reviews all technological issues regarding IDDS implantation with follow-up, and pharmacological recommendations published during recent years that provide evidence-based decision making process in the management of chronic pain and spasticity in patients. PMID:24567144

  17. Liposomal cytarabine for leukemic and lymphomatous meningitis: recent developments.

    PubMed

    Benesch, Martin; Urban, Christian

    2008-02-01

    Liposomal cytarabine (Depocyte) is a sustained-release formulation of cytarabine developed for intrathecal administration, ensuring prolonged cytotoxic drug concentrations of cytarabine in cerebrospinal fluid. Although liposomal cytarabine is increasingly used for the treatment (and prophylaxis) of CNS involvement in patients with leukemia/lymphoma, many of the recently presented clinical trials on liposomal cytarabine were retrospective in nature or used this drug on a compassionate basis. So far, one randomized Phase III study has shown significantly better response rates in patients with lymphomatous meningitis who received liposomal cytarabine compared with free cytarabine. Considerable concerns about the safety of this drug arose from recent observations that liposomal cytarabine might contribute to neurologic side effects when given too closely to high-dose systemic chemotherapy known to penetrate the brain-blood barrier. Superior efficacy of liposomal cytarabine compared with standard intrathecal therapy should be confirmed in prospective clinical trials. Careful adherence with preventive measures might help physicians to minimize side effects possibly related to the administration of liposomal cytarabine. PMID:18201152

  18. Long-acting injectable hormonal dosage forms for contraception.

    PubMed

    Wu, Linfeng; Janagam, Dileep R; Mandrell, Timothy D; Johnson, James R; Lowe, Tao L

    2015-07-01

    Although great efforts have been made to develop long-acting injectable hormonal contraceptives for more than four decades, few long-acting injectable contraceptives have reached the pharmaceutical market or even entered clinical trials. On the other hand, in clinical practice there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after one single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics. Herein, we reviewed the strategies exploited in the past to develop injectable hormonal contraceptive dosages including drug microcrystal suspensions, drug-loaded microsphere suspensions and in situ forming depot systems for long-term contraception and discussed the potential solutions for remaining issues met in the previous development. PMID:25899076

  19. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications. PMID:6114503

  20. Intrathecal Baclofen Pump for Spasticity

    PubMed Central

    2005-01-01

    Executive Summary Objective To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity. The Technology Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is

  1. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development. PMID:26187188

  2. Two cases of long-acting paliperidone in adolescence

    PubMed Central

    Fàbrega, Marina; Sugranyes, Gisela; Baeza, Inmaculada

    2015-01-01

    Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance. PMID:26557986

  3. Comparative effectiveness of long-acting antipsychotics: issues and challenges from a pragmatic randomised study.

    PubMed

    Ostuzzi, G; Barbui, C

    2016-02-01

    Although long-acting antipsychotics are widely used in individuals with psychotic disorders, it is unclear which long-acting preparation should be considered as first-line treatment in clinical practice. In this commentary, the main strengths and weaknesses of a recently published pragmatic randomised study comparing long-acting paliperidone palmitate v. long-acting haloperidol decanoate are briefly analysed. PMID:26515607

  4. The pharmacokinetics of long-acting antipsychotic medications.

    PubMed

    Spanarello, Stefano; La Ferla, Teresa

    2014-01-01

    The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate. The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine undecylenate, pipotiazine palmitate, fluspirilene, long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, long-acting iloperidone, long-acting injectable aripiprazole) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. PMID:23343447

  5. Inadvertent intrathecal injection of labetalol.

    PubMed

    Verma, S; Bhatia, P K; Sharma, V; Sethi, P

    2016-01-01

    Labetalol is a combined α and β adrenergic receptor blocker. It is used to treat hypertension, especially in pregnant patients. We report a case of a female patient who was given labetalol intrathecally in place of bupivacaine due to a similar appearance of ampoules which resulted in a drop in blood pressure and pulse rate. The patient responded to fluid resuscitation and there occurred no neurological sequelae. PMID:27375395

  6. Inadvertent intrathecal injection of labetalol

    PubMed Central

    Verma, S; Bhatia, PK; Sharma, V; Sethi, P

    2016-01-01

    Labetalol is a combined α and β adrenergic receptor blocker. It is used to treat hypertension, especially in pregnant patients. We report a case of a female patient who was given labetalol intrathecally in place of bupivacaine due to a similar appearance of ampoules which resulted in a drop in blood pressure and pulse rate. The patient responded to fluid resuscitation and there occurred no neurological sequelae. PMID:27375395

  7. A qualitative analysis of long-acting reversible contraception.

    PubMed

    Sundstrom, Beth; Baker-Whitcomb, Annalise; DeMaria, Andrea L

    2015-07-01

    Increasing access to long-acting reversible contraception (LARC), including the intrauterine device and the implant is a public health and clinical imperative to reduce rates of unintended pregnancy. In 2012, the American College of Obstetricians and Gynecologists recommended these methods for all women, including adolescents. Little research explores why young women reject these safe, effective contraceptive methods. A total of 53 women aged 18-24 years completed in-depth interviews. Analytical techniques from the grounded theory approach were used to identify patterns and themes across the data. Participants initiated hormonal contraception for "the pill's" beneficial side effects and believed a myth of perfect use, which constructed a false choice of LARC methods. Barriers to LARC options included access, medical resistance, and cost. Participants described a sense of unease about methods perceived as "alien." These women underestimated the risks of oral contraceptive pills and overestimated the risks of long-acting reversible contraception, including infertility. The myth of perfect use emerged as participants wanted to be in control by taking "the pill" every day; however, many described imperfect adherence. Findings include strategies for public health professionals and health care providers to distribute satisfactory and effective contraception for young women. Effective health communication campaigns will emphasize the desirable side effects, safety and increased effectiveness of LARC methods. PMID:25424456

  8. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes

    PubMed Central

    Edagwa, Benson J.; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E.; Narayanasamy, Prabagaran

    2014-01-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.—Edagwa, B. J., Guo, D., Puligujja, P., Chen, H., McMillan, J., Liu, X., Gendelman, H. E., Narayanasamy, P. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. PMID:25122556

  9. Access Barriers to Long-Acting Reversible Contraceptives for Adolescents.

    PubMed

    Kumar, Natasha; Brown, Joanna D

    2016-09-01

    The United States continues to have the highest adolescent birth rate of any industrialized country. Recently published guidelines by the American Academy of Pediatrics create a new consensus among professional organizations around the suitability of long-acting reversible contraceptives as first-line contraception for adolescents. Through a narrative review of U.S. studies published after 2000, this study seeks to summarize existing access barriers to long-acting reversible contraceptives for adolescents and highlight areas that warrant further intervention so that the recommendations of these professional organizations can be effectively integrated into clinical practice. Existing barriers include costs for institutions providing contraceptive care and for recipients; consent and confidentiality for adolescent patients; providers' attitudes, misconceptions and limited training; and patients' lack of awareness or misconceptions. Systemic policy interventions are required to address cost and confidentiality, such as the Affordable Care Act's mandate that contraceptive coverage be a part of essential health benefits for all insurance providers. Individual-level access barriers such as providers' misconceptions and gaps in technical training as well as patients' lack of awareness can be addressed directly by professional medical organizations, health care training programs, and other interventions. PMID:27247239

  10. Intrathecal drug administration in chronic pain syndromes.

    PubMed

    Ver Donck, Ann; Vranken, Jan H; Puylaert, Martine; Hayek, Salim; Mekhail, Nagy; Van Zundert, Jan

    2014-06-01

    Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long-term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo-controlled trials. A randomized study showed this treatment option to be effective over a short follow-up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drug administration in patients suffering from cancer-related pain is more compelling than that of chronic noncancer pain. PMID:24118774

  11. Doped colorimetric assay liposomes

    DOEpatents

    Charych, Deborah; Stevens, Raymond C.

    2001-01-01

    The present invention provides compositions comprising colorimetric assay liposomes. The present invention also provides methods for producing colorimetric liposomes and calorimetric liposome assay systems. In preferred embodiments, these calorimetric liposome systems provide high levels of sensitivity through the use of dopant molecules. As these dopants allow the controlled destabilization of the liposome structure, upon exposure of the doped liposomes to analyte(s) of interest, the indicator color change is facilitated and more easily recognized.

  12. P08.19PRIMARY INTRATHECAL MELANOMA ARISING FROM MENINGEAL MELANOCYTOSIS: A CASE REPORT

    PubMed Central

    Moser, W.; Thier, K.; Hafner, C.; Trautinger, F.; Ungersböck, K.; Sedivy, R.; Oberndorfer, S.

    2014-01-01

    INTRODUCTION: Primary melanocytic tumours of the leptomeninges are rare diseases. The WHO classification of 2007 described four entities: diffuse melanocytosis, melanocytoma, malignant melanoma and meningeal melanomatosis. Meningeal melanocytosis is a benign proliferation of melanocytes with a risk of malignant transformation and is often associated with neurocutaneos melanosis. CASE REPORT: A 65-year-old male patient presented with low back pain and disturbed micturition. Neurological examination revealed left sided S1- sensory radiculopathy. His medical history was unremarkable. MRI of the lumbar spine showed a contrast-enhancing intrathecal tumour of the conus medullaris and MRI of the brain was suspicious of neoplastic meningitis. Spinal surgery exhibited a brown tumour mass with diffuse spreading of pigmented lesions along the arachnoidea. Histological, immunohistochemical, and molecular analyses showed an intrathecal melanoma with a wild-type BRAF genotype. Dermatological examination was unremarkable. Lumbar stereotactic radiotherapy was applied. Subsequently, 3 cycles of temozolomide (150mg/m2 on 5 days out of 28) and bi-weekly intrathecal liposomal cytarabine were administered. Despite the poor prognosis of neoplastic meningitis in melanoma, the patient survived without clinical for more than one year. 15 months after the initial diagnosis spinal MRI showed a local relapse and a second surgery was performed. This time molecular analysis of the tumor revealed the presence of the BRAF V600E mutation. Due to the initially slow tumor progression treatment with B-Raf inhibitors was withheld and immunotherapy with the anti-CTLA-4 antibody ipilimumab was initiated together with stereotactic radiotherapy of the conus medullaris. Three months later, the patient complained about diplopia and dizziness. Neurological examination revealed oculomotor nerve palsy. MRI of the brain showed a meningeal contrast-enhancement in the brainstem area. The B-Raf inhibitor

  13. CE: Intrathecal Pumps for Managing Cancer Pain.

    PubMed

    Textor, Laura Hanssen

    2016-05-01

    : It is estimated that more than 1.6 million new cases of cancer were diagnosed in the United States in 2014. Among patients with cancer, moderate to severe pain is prevalent and can be refractory, even with the use of systemic opioids, which may cause adverse effects that are difficult to manage at the doses required to control pain. When delivered intrathecally, however, opioids and adjuvant analgesics may provide greater pain relief at dramatically lower doses and with fewer adverse effects. Although the use of intrathecal drug delivery systems for cancer pain management has increased dramatically over the past several years and is expected to continue growing, patients with intrathecal pumps often report interactions with nurses unfamiliar with the technology. This article provides an overview of intrathecal pump therapy and explains how it prolongs duration of action and improves the efficacy of certain analgesics while reducing their adverse effects. The author discusses the costs involved, the patients most likely to derive benefit, the types of pumps currently used in the United States, the medications that can be delivered intrathecally, the potential risks and complications associated with intrathecal therapy, and the nursing care required by patients who use an intrathecal pump. PMID:27082422

  14. Long-Acting Reversible Contraception (LARC) for Adolescent

    PubMed Central

    McNicholas, Colleen; Peipert, Jeffrey F

    2014-01-01

    Purpose of review Teen pregnancy continues to plague the United States. This review will discuss long-acting reversible contraceptive (LARC) method use in teens. It will specifically address the myths about appropriate candidates as well as continuation and satisfaction among teen users. Recent findings The American College of Obstetrics and Gynecology along with the American Academy of Pediatrics, the Centers for Disease Control, and the World health Organization have recognized the potential impact of LARC (comprising intrauterine contraception and subdermal implants) to reduce unintended pregnancies. They have affirmed the safety of such devices, and no effects on long-term fertility have been identified. Teen users of these methods have been shown to have high continuation and satisfaction rates. On the other hand, oral contraceptive pills, the patch, and the contraceptive vaginal ring have significantly higher contraceptive failure rates, and these rates are magnified in young women. Summary LARC methods should be considered first-line options for teens seeking contraception. PMID:22781078

  15. Efficacy and Safety of Long-Acting Reversible Contraception

    PubMed Central

    Stoddard, Amy; McNicholas, Colleen; Peipert, Jeffrey F.

    2013-01-01

    Long-acting reversible contraception (LARC) includes intrauterine devices (IUDs) and the subdermal implant. These methods are the most effective reversible methods of contraception, and have the additional advantages of being long-lasting, convenient, well liked by users and cost effective. Compared with other user-dependent methods that increase the risk of noncompliance-related method failure, LARC methods can bring ‘typical use’ failure rates more in line with ‘perfect use’ failure rates. LARC methods are ‘forgettable’; they are not dependent on compliance with a pill-taking regimen, remembering to change a patch or ring, or coming back to the clinician for an injection. LARC method failure rates rival that of tubal sterilization at <1% for IUDs and the subdermal implant. For these reasons, we believe that IUDs and implants should be offered as first-line contraception for most women. This article provides a review of the LARC methods that are currently available in the US, including their effectiveness, advantages, disadvantages and contraindications. Additionally, we dispel myths and misconceptions regarding IUDs, and address the barriers to LARC use. PMID:21668037

  16. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  17. Long-Acting Beta Agonists Enhance Allergic Airway Disease.

    PubMed

    Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  18. Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

    PubMed

    Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

    2016-01-01

    Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation. PMID:27074333

  19. Intrathecal Veratridine Administration Increases MAC in Rats

    PubMed Central

    Zhang, Yi; Sharma, Manohar; Eger, Edmond I; Laster, Michael J.; Hemmings, Hugh C.; Harris, R. Adron

    2008-01-01

    Background Results from several studies point to sodium channels as potential mediators of the immobility produced by inhaled anesthetics. We hypothesized that the intrathecal administration of veratridine, a drug that enhances the activity or effect of sodium channels, should increase MAC. Methods We measured the change in isoflurane MAC caused by intrathecal infusion of various concentrations of veratridine into the lumbothoracic subarachnoid space of rats. We compared these result to those obtained from intracerebroventricular infusion. Results As predicted, intrathecal infusion of veratridine increased MAC. The greatest infused concentration (25 μM) also produced neuronal injury in the hind limbs of two rats and decreased the peak effect on MAC. A concentration of 1.6 μM produced the greatest (21%) increase in MAC. Intraventricular infusion of 1.6 and 6.4 μM veratridine did not alter MAC. Rats given 25 μM died. Conclusion Intrathecal administration of veratradine increases MAC of isoflurane, a finding consistent with a role for sodium channels as potential mediators of the immobility produced by inhaled anesthetics. Implications Intrathecal administration of veratridine can increase MAC, presumably by an effect on sodium channels. PMID:18713899

  20. Gold liposomes

    SciTech Connect

    Hainfeld, J.F.

    1996-12-31

    Lipids are an important class of molecules, being found in membranes, HDL, LDL, and other natural structures, serving essential roles in structure and with varied functions such as compartmentalization and transport. Synthetic liposomes are also widely used as delivery and release vehicles for drugs, cosmetics, and other chemicals; soap is made from lipids. Lipids may form bilayer or multilammellar vesicles, micelles, sheets, tubes, and other structures. Lipid molecules may be linked to proteins, carbohydrates, or other moieties. EM study of this essential ingredient of life has lagged, due to lack of direct methods to visualize lipids without extensive alteration. OsO4 reacts with double bonds in membrane phospholipids, forming crossbridges. This has been the method of choice to both fix and stain membranes, thus far. An earlier work described the use of tungstate clusters (W{sub 11}) attached to lipid moieties to form lipid structures and lipid probes. With the development of gold clusters, it is now possible to covalently and specifically link a dense gold sphere to a lipid molecule; for example, reacting a mono-N-hydroxysuccinimide Nanogold cluster with the amino group on phosphatidyl ethanolaminine. Examples of a gold-fatty acid and a gold-phospholipid are shown.

  1. Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report.

    PubMed

    Gaviani, Paola; Silvani, A; Corsini, E; Erbetta, A; Salmaggi, A

    2009-06-01

    Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte). PMID:19259616

  2. Liposome technology. Volume I: Preparation of liposomes

    SciTech Connect

    Gregoriadis, G.

    1984-01-01

    These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume I examine methods for the preparation of liposomes and auxiliary techniques.

  3. Current perspectives on intrathecal drug delivery

    PubMed Central

    Bottros, Michael M; Christo, Paul J

    2014-01-01

    Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

  4. Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine.

    PubMed

    Kripp, Melanie; Hofheinz, Ralf-Dieter

    2008-01-01

    Liposomal encapsulated cytarabine (DepoCyte, Mundipharma GmbH, Limburg/Lahn, Germany) is a slow-release formulation of conventional cytarabine. It is licensed for intrathecal use in patients with lymphomatous and leukemic meningitis. DepoCyte obtained superior response rates, improved patient quality of life and improved the time to neurological progression in a randomized albeit small clinical trial. In this review we briefly summarize the clinical data and discuss them in light of clinical problems and possible treatment scenarios. PMID:19337408

  5. Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine

    PubMed Central

    Kripp, Melanie; Hofheinz, Ralf-Dieter

    2008-01-01

    Liposomal encapsulated cytarabine (DepoCyte®, Mundipharma GmbH, Limburg/Lahn, Germany) is a slow-release formulation of conventional cytarabine. It is licensed for intrathecal use in patients with lymphomatous and leukemic meningitis. DepoCyte® obtained superior response rates, improved patient quality of life and improved the time to neurological progression in a randomized albeit small clinical trial. In this review we briefly summarize the clinical data and discuss them in light of clinical problems and possible treatment scenarios. PMID:19337408

  6. Aneurysm, arachnoiditis and intrathecal Au (gold)

    SciTech Connect

    Pence, D.M.; Kim, T.H.; Levitt, S.H. )

    1990-05-01

    This report is a 20-year follow-up of 14 patients treated with external beam craniospinal irradiation and intrathecal gold (10-45 mCi) for medulloblastoma. Six of the patients died within 2 years of treatment from persistent disease. No patients are alive without complications. Six of eight surviving patients developed arachnoiditis and cauda equina syndrome within 5 to 10 years of treatment. Seven of eight survivors developed aneurysms and/or cerebrovascular accidents 9 to 20 years after treatment. Four of the cerebrovascular events were fatal. Intrathecal gold pools in the basal cisterns and cauda equina delivering an extremely inhomogeneous dose throughout the neuroaxis. Its use is discouraged.

  7. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease

    PubMed Central

    Karner, Charlotta; Cates, Christopher J

    2014-01-01

    Background Long-acting bronchodilators comprising long-acting beta2-agonists and the anticholinergic agent tiotropium are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary (COPD) disease are unclear. Objectives To assess the relative effects of treatment with tiotropium in addition to long-acting beta2-agonist compared to tiotropium or long-acting beta2-agonist alone in patients with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials and clinicaltrials.gov up to January 2012. Selection criteria We included parallel group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to long-acting beta2-agonist against tiotropium or long-acting beta2-agonist alone for patients with chronic obstructive pulmonary disease. Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results Five trials were included in this review, mostly recruiting participants with moderate or severe chronic obstructive pulmonary disease. All of them compared tiotropium in addition to long-acting beta2-agonist to tiotropium alone, but only one trial additionally compared a combination of the two types of bronchodilator with long-acting beta2-agonist (formoterol) alone. Two studies used the long-acting beta2-agonist indacaterol, two used formoterol and one used salmeterol. Compared to tiotropium alone (3263 patients), treatment with tiotropium plus long-acting

  8. Liposomes as nanomedical devices

    PubMed Central

    Bozzuto, Giuseppina; Molinari, Agnese

    2015-01-01

    Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials. PMID:25678787

  9. Intrathecal Baclofen Therapy: Benefits and Complications

    ERIC Educational Resources Information Center

    Zdolsek, Helena Aniansson; Olesch, Christine; Antolovich, Giuliana; Reddihough, Dinah

    2011-01-01

    Background: Spasticity and dystonia in children with cerebral palsy has been treated with intrathecal baclofen therapy (ITB) at the Royal Children's Hospital, Melbourne, Australia (RCH) since 1999. Methods: The records of children having received or still receiving ITB during the period September 1999 until August 2005 were studied to evaluate…

  10. Long-Acting Injectable Naltrexone for the Management of Patients with Opioid Dependence

    PubMed Central

    Kjome, Kimberly L.; Moeller, F. Gerard

    2011-01-01

    Opioid dependence is a condition with serious clinical ramifications. Treatment has focused on detoxification, agonist therapy with methadone or buprenorphine, or remission maintenance with the opioid antagonist, naltrexone. Treatment with oral naltrexone has been limited by poor treatment adherence and relapse. Studies with long-acting formulations have shown increased treatment adherence. Extended-release injectable naltrexone has been used for the treatment of alcohol dependence, and has recently received an indication for treatment of opioid dependence from the US Food and Drug Administration. Dosing occurs once monthly and existing data with long-acting naltrexone supports efficacy of treatment for opioid dependence; however published data is sparse. Treatment with long-acting naltrexone should be monitored for hepatotoxicity, and patients should be made aware of increased risk of overdose with administration of opioids during and immediately after discontinuation of long-acting naltrexone. PMID:22879745

  11. Committee Opinion No 672 Summary Clinical Challenges of Long-Acting Reversible Contraceptive Methods.

    PubMed

    2016-09-01

    Long-acting reversible contraceptive methods are the most effective reversible contraceptives and have an excellent safety record. Although uncommon, possible long-acting reversible contraceptive complications should be included in the informed consent process. Obstetrician-gynecologists and other gynecologic care providers should understand the diagnosis and management of common clinical challenges. The American College of Obstetricians and Gynecologists recommends the algorithms included in this document for management of the most common clinical challenges. PMID:27548551

  12. Committee Opinion No 672: Clinical Challenges of Long-Acting Reversible Contraceptive Methods.

    PubMed

    2016-09-01

    Long-acting reversible contraceptive methods are the most effective reversible contraceptives and have an excellent safety record. Although uncommon, possible long-acting reversible contraceptive complications should be included in the informed consent process. Obstetrician-gynecologists and other gynecologic care providers should understand the diagnosis and management of common clinical challenges. The American College of Obstetricians and Gynecologists recommends the algorithms included in this document for management of the most common clinical challenges. PMID:27548557

  13. Recent advances in COPD disease management with fixed-dose long-acting combination therapies.

    PubMed

    Bateman, Eric D; Mahler, Donald A; Vogelmeier, Claus F; Wedzicha, Jadwiga A; Patalano, Francesco; Banerji, Donald

    2014-06-01

    Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β2-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD. PMID:24802656

  14. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  15. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  16. Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

    PubMed

    Minor, B G; Persson, M L; Post, C; Jonsson, G; Archer, T

    1988-01-01

    Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia. PMID:3133452

  17. Multi-liposomal containers.

    PubMed

    Yaroslavov, A A; Sybachin, A V; Zaborova, O V; Zezin, A B; Talmon, Y; Ballauff, M; Menger, F M

    2015-12-01

    Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL(2-)) or phosphatidylcerine (PS(1-)) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains ("spherical polycationic brushes", SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometry, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo-TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into "islands". (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as ν) that ensures the structural integrity of liposomes upon complexation: ν=0.3 for liposomes with conically-shaped CL(2-) and ν=0.5 for liposomes with anionic cylindrically-shaped PS(1-). (c) The number of intact liposomes per SPB particle varies from 40 for (ν=0.1) to 13 (ν=0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents

  18. Intrathecal Drug Delivery (ITDD) systems for cancer pain

    PubMed Central

    Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

    2014-01-01

    Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

  19. Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia.

    PubMed

    Chen, Wen-Yin; Lin, Shih-Ku

    2016-10-01

    We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted. PMID:27580495

  20. Nasal absorption of mixtures of fast-acting and long-acting insulins

    PubMed Central

    Pillion, Dennis J.; Fyrberg, Michael D.; Meezan, Elias

    2010-01-01

    Mixtures of fast-acting and long-acting insulins were administered nasally to anesthetized, hyperglycemic rats in the presence and absence of tetradecyl-β-D-maltoside (TDM). The fast-acting analogs, aspart insulin, lispro insulin, and glulisine insulin, were all rapidly absorbed from the nose when applied individually with 0.125% TDM (Tmax = 15 minutes). One long-acting insulin analog, glargine insulin, was also absorbed from the nose when applied individually in the presence of 0.125% TDM (Tmax = 60 minutes). The other long-acting insulin analog, detemir insulin, was not soluble when formulated with 0.125% TDM. A series of mixtures (1:1) of the three rapid-acting insulins and long-acting glargine insulin were formulated with 0.125% TDM and applied nasally. The pharmacokinetic and pharmacodynamic profiles of the insulin mixtures reflected the additive contributions of both the rapid-acting and the long-acting insulin. These results support the possibility of formulating certain insulin mixtures in tandem to provide nasal insulin products that match the needs of patients with diabetes mellitus better than those currently available. PMID:20080164

  1. Fused liposome and acid induced method for liposome fusion

    SciTech Connect

    Huang, L.; Connor, J.

    1988-12-06

    This patent describes a method of fusing liposomes. It comprises: preparing a suspension of liposomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least 20 mol percent of palmitoylhomocysteine; and in the absence of externally added divalent cations, proteins or other macromolecules, acidifying the liposome suspension to reduce the pH of the liposomes to below pH 7, such that at least about 20% of the liposomes fuse to one another.

  2. The Impact of Long-Acting Medications on Attention-Deficit/Hyperactivity Disorder Treatment Disparities

    PubMed Central

    Fullerton, Catherine; McGuire, Thomas

    2013-01-01

    Abstract Objective Long-acting stimulants have increased medication adherence for many children diagnosed with attention deficit/hyperactivity disorder (ADHD), but it is unknown whether the increase has been similar across racial/ethnic groups. Our objective was to determine whether differences in medication utilization and adherence among white, black, and Hispanic ADHD-diagnosed children and adolescents narrowed following the introduction of long-acting stimulants in the 1990s. Methods We conducted a retrospective analysis of Florida Medicaid claims data from fiscal years 1996–2005. At each of three cross sections, we identified children and adolescents 3–17 years of age with at least two claims with an ADHD diagnosis. We used linear regression to model disparities over the study period in utilization of any ADHD medications (utilization of long-acting medication specifically) and medication adherence, and identified patient level, treatment setting, and geographic contributors to disparities. Results Although ADHD medication utilization was lower for ADHD-diagnosed minorities than whites in all years, minorities were as likely as whites to switch to long-acting medications. The increase in prescribed days following long-acting medication diffusion was comparable for white and black medication users (40 and 43 days, respectively), but lower for Hispanics (27 days). Geography and provider setting helped to explain disparities in medication utilization overall, but disparities in adherence were not explained by any of the covariates. Conclusions Despite equivalent switching to long-acting medications in the study period, minorities continued to utilize all ADHD medications less than did whites, and for shorter periods. Provider setting helps explain the ADHD medication utilization gap. High-volume, minority-serving providers are potential targets for future interventions related to improved communication about medication and follow-up after medication

  3. Use of Aripiprazole Long Acting Injection in Negative Symptoms of Schizophrenia.

    PubMed

    James, Suneeta; Kapugama, Chaya; Al-Uzri, Mohammed

    2016-01-01

    Background. Evidence for the efficacious use of second-generation antipsychotics for the treatment of negative symptoms in schizophrenia is scant. Case Presentation. We report the case of a 34-year-old female of Afro-Caribbean origin, who presented with prominent negative symptoms of schizophrenia and was successfully treated with aripiprazole long acting injection. Within a period of six to nine months, the patient returned to her premorbid level of functioning. Conclusion. Aripiprazole long acting injection promises benefits in the treatment of negative symptoms of schizophrenia. Further research needs to be conducted on the use of this drug. PMID:26981301

  4. Use of Aripiprazole Long Acting Injection in Negative Symptoms of Schizophrenia

    PubMed Central

    James, Suneeta; Kapugama, Chaya; Al-Uzri, Mohammed

    2016-01-01

    Background. Evidence for the efficacious use of second-generation antipsychotics for the treatment of negative symptoms in schizophrenia is scant. Case Presentation. We report the case of a 34-year-old female of Afro-Caribbean origin, who presented with prominent negative symptoms of schizophrenia and was successfully treated with aripiprazole long acting injection. Within a period of six to nine months, the patient returned to her premorbid level of functioning. Conclusion. Aripiprazole long acting injection promises benefits in the treatment of negative symptoms of schizophrenia. Further research needs to be conducted on the use of this drug. PMID:26981301

  5. Long-acting Preparations in Substance Abuse Management: A Review and Update

    PubMed Central

    Hegde, Aditya; Singh, Shubh Mohan; Sarkar, Siddharth

    2013-01-01

    Many pharmacological approaches have been used in managing substance use disorders. Conventional pharmacological agents have relatively short durations of action which make them vulnerable to non-adherence and relapse to substance use disorder. To overcome this problem, long-acting preparations have been developed with the aim of reducing the frequency of use and hence improving adherence. This review takes a broad overview of the long-acting preparations available for the management of substance use disorders. The pharmacology, advantages and disadvantages of these preparations are discussed. Many of these preparations hold promise for improving patient outcomes. PMID:23833336

  6. Liposome formation in microgravity

    NASA Astrophysics Data System (ADS)

    Claassen, D. E.; Spooner, B. S.

    Liposomes are artificial vesicles with a phospholipid bilayer membrane. The formation of liposomes is a self-assembly process that is driven by the amphipathic nature of phospholipid molecules and can be observed during the removal of detergent from phospholipids dissolved in detergent micelles. As detergent concentration in the mixed micelles decreases, the non-polar tail regions of phospholipids produce a hydrophobic effect that drives the micelles to fuse and form planar bilayers in which phospholipids orient with tail regions to the center of the bilayer and polar head regions to the external surface. Remaining detergent molecules shield exposed edges of the bilayer sheet from the aqueous environment. Further removal of detergent leads to intramembrane folding and membrane vesiculation, forming liposomes. We have observed that the formation of liposomes is altered in microgravity. Liposomes that were formed at 1-g did not exceed 150 nm in diameter, whereas liposomes that were formed during spaceflight exhibited diameters up to 2000 nm. Using detergent-stabilized planar bilayers, we determined that the stage of liposome formation most influenced by gravity is membrane vesiculation. In addition, we found that small, equipment-induced fluid disturbances increased vesiculation and negated the size-enhancing effects of microgravity. However, these small disturbances had no effect on liposome size at 1-g, likely due to the presence of gravity-induced buoyancy-driven fluid flows (e.g., convection currents). Our results indicate that fluid disturbances, induced by gravity, influence the vesiculation of membranes and limit the diameter of forming liposomes.

  7. Bilateral internuclear ophthalmoplegia after intrathecal chemotherapy and cranial irradiation

    SciTech Connect

    Lepore, F.E.; Nissenblatt, M.J.

    1981-12-01

    A 26-year-old man developed transient bilateral internuclear ophthalmoplegia with exotropia after cranial irradiation and intrathecal administration of methotrexate for lymphoma. Resolution of the ophthalmoplegia and the decrease in abnormally high levels of cerebrospinal fluid myelin basic protein after discontinuation of intrathecal medication suggested demyelination from chemotherapy and irradiation.

  8. Staphylococcal meningitis following Synchromed intrathecal pump implant: a case report.

    PubMed

    Bennett, M I; Tai, Y M; Symonds, J M

    1994-02-01

    Staphylococcal meningitis associated with implantation of an intrathecal drug pump for spasticity was successfully treated by intrathecal vancomycin delivered by the same pump. This produced high CSF antibiotic levels, and the pump and catheter system did not have to be removed. We are unable to identify a similar case reported in the literature to date. PMID:8008414

  9. Pharmacokinetics of Short- and Long-acting Formulations of Oxytetracycline After Intramuscular Administration in Chickens.

    PubMed

    Gberindyer, Aondover F; Okpeh, Ene R; Semaka, Asaaga A

    2015-12-01

    Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions. Fourteen chickens were separated into 2 groups: chickens in group A (n = 7) were administered the short-acting formulation (10 mg/kg IM q24h) for 4 consecutive days, whereas those in group B (n = 7) were treated with a single dose (20 mg/kg IM) of the long-acting formulation. Blood samples were collected into heparinized tubes before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 24 hours after initial treatment. Thereafter, blood samples were taken every 24 hours up to 120 hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. Both formulations delivered therapeutic plasma concentrations of oxytetracycline for approximately 100% of their respective dosing intervals as recommended. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens. PMID:26771319

  10. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    ERIC Educational Resources Information Center

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  11. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  12. Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists have both glucose- and weight-lowering effects. The brain is poised to mediate both of these actions since GLP-1Rs are present in key areas known to control weight and glucose. Although some research has been performed on the effects of ...

  13. Long-acting muscarinic antagonist + long-acting beta agonist versus long-acting beta agonist + inhaled corticosteroid for COPD: A systematic review and meta-analysis.

    PubMed

    Horita, Nobuyuki; Miyazawa, Naoki; Tomaru, Koji; Inoue, Miyo; Kaneko, Takeshi

    2015-11-01

    Some trials have been conducted to compare long-acting muscarinic antagonist (LAMA) + long-acting beta agonist (LABA) versus LABA + inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), but no meta-analysis were reported. Two investigators independently searched for eligible articles using the PubMed, Web of Science and Cochrane databases. Articles in authors' reference files were also regarded as candidates. The eligibility criteria for the current meta-analysis were original trials written in English comparing the impact of LAMA + LABA and LABA + ICS for COPD patients. A pooled value for the continuous value was calculated using the genetic inverse variance method for mean difference. Incidence of events was evaluated using the odds ratio (OR). Minimal clinically important difference were 50 mL for forced expiratory volume in 1 s (FEV1 ), four points for St George Respiratory Questionnaire (SGRQ) and one point for transition dyspnoea index (TDI). We included seven randomized controlled trials and one cross-over trial with follow-up period of 6-26 weeks. Compared with LABA + ICS, LAMA + LABA led to significantly greater improvements of trough FEV1 by 71 (95% CI: 48-95) mL, TDI by 0.38 points (95% CI: 0.17-0.58), less exacerbations with an OR of 0.77 (95% CI: 0.62-0.96) and less pneumonia with an OR of 0.28 (95% CI: 0.12-0.68). Frequencies of any adverse event, serious adverse event, adverse event leading to discontinuation, all-cause death and change of total score of SGRQ were not different in both arms. LAMA + LABA might be a better option for treating COPD than LABA + ICS. PMID:26235837

  14. Patient perspectives in the development and use of long-acting antipsychotics in schizophrenia: focus on olanzapine long-acting injection

    PubMed Central

    Citrome, Leslie

    2009-01-01

    Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable “depot” preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection. PMID:20016798

  15. Patient perspectives in the development and use of long-acting antipsychotics in schizophrenia: focus on olanzapine long-acting injection.

    PubMed

    Citrome, Leslie

    2009-01-01

    Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable "depot" preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection. PMID:20016798

  16. Switching from risperidone long-acting injectable to paliperidone long-acting injectable or oral antipsychotics: analysis of a Medicaid claims database

    PubMed Central

    Ryan, Patrick B.; Stang, Paul E.; Hough, David; Alphs, Larry

    2015-01-01

    This report examines relapse risk following a switch from risperidone long-acting injectable (RLAI) to another long-acting injectable antipsychotic [paliperidone palmitate (PP)] versus a switch to oral antipsychotics (APs). Truven Health’s MarketScan Multistate Medicaid Database compared relapses following switches from RLAI. New user cohorts for these two groups were created on the basis of first incidence of exposure to the ‘switched to’ drug. Groups were balanced using 1:1 propensity score matching. Time-to-event analysis assessed schizophrenia-related hospital/emergency department visits. A total of 188 patients switched from RLAI to PP, and 131 patients switched from RLAI to oral AP. Propensity score-matched cohort included 109 patients who switched to PP and 109 patients who switched to an oral AP. Patients who switched from RLAI to PP had fewer events (26 vs. 32), longer time to an event (mean 70 vs. 47 days), and lower risk of relapse (hazard ratio, 0.54; 95% confidence interval, 0.32–0.92; P=0.024) compared with those who switched from RLAI to oral AP. Switching from RLAI to PP may be associated with a lower risk for relapse and longer duration of therapy compared with switching to oral AP. Given the limitations of observational studies, these results should be confirmed by other prospective evaluations. PMID:25730525

  17. Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

    PubMed Central

    Price, David; Fromer, Leonard; Kaplan, Alan; van der Molen, Thys; Román-Rodríguez, Miguel

    2014-01-01

    Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of ‘cholinergic tone’. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations. PMID:25030457

  18. Long-acting injectable antipsychotics in the elderly: guidelines for effective use.

    PubMed

    Masand, Prakash S; Gupta, Sanjay

    2003-01-01

    The elderly are at increased risk for psychosis because of age-related deterioration of cortical areas and neurochemical changes, comorbid physical illnesses, social isolation, sensory deficits and polypharmacy. The prevalence of psychiatric and neuropsychiatric disorders requiring treatment with an antipsychotic agent is expected to increase dramatically among people aged >64 years. Antipsychotic agents are effective in the treatment of schizophrenia, schizoaffective disorder, behavioural symptoms in patients with dementia, and mood disorders with psychosis. However, failure to adhere to a prescribed medication regimen by patients with psychosis is one of the most frustrating problems faced by mental healthcare providers, because of the high risk of relapse associated with partial compliance. For patients with psychosis who will not or cannot take oral medications on a regular daily basis or have other characteristics, such as memory, vision or auditory impairment, which contribute to partial compliance, long-acting injectable antipsychotic medication offers a solution. Older patients are especially at risk of adverse effects associated with traditional antipsychotic agents, such as motor effects, postural hypotension, excessive sedation, and anticholinergic effects because of age-related pharmacokinetic and pharmacodynamic factors, coexisting medical illnesses and concomitant medications. Therefore, drug dosage recommendations in the elderly are much more conservative than in younger patients. The appropriate starting dose of an antipsychotic in older individuals is 25% of the usual adult dose; total daily maintenance doses ranges from 25-50% of the adult dose. There are few studies regarding the use of depot antipsychotics in elderly patients. Studies that are available indicate that traditional antipsychotic agents given as depot injections are associated with positive outcomes in the elderly. Because the risks for extrapyramidal symptoms and tardive dyskinesia

  19. [Meningeal tertiary lymphoid organs: Major actors in intrathecal autoimmunity].

    PubMed

    Bonnan, M

    2015-01-01

    Multiple sclerosis (MS) is characterized by an intrathecal synthesis of immunoglobulins synthesized by B-cell clones and by a brain infiltrate of clonal T-cells. The clonal maturation of these lymphocytes takes place in tertiary lymphoid organs (TLO) developed in the intrathecal compartment. TLO are acquired lymphoid organs able to develop in the vicinity of the inflammatory sites, where they mount a complete antigen-driven immune response. We here review TLO pathophysiology in animal models of MS and human MS. Several pieces of evidence suggest that intrathecal TLO may play a major role in the clinical impairment. Potential therapeutic applications are examined. PMID:25555848

  20. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly.

    PubMed

    Chang, Jan-Shun; Tseng, Ham-Min; Chang, Tien-Chun

    2016-06-01

    The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR) and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration. PMID:27117887

  1. Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early

  2. Viscoelasticity measurements inside liposomes

    NASA Astrophysics Data System (ADS)

    Zhang, Shu; Gibson, Lachlan; Preece, Daryl; Nieminen, Timo A.; Rubinsztein-Dunlop, Halina

    2014-09-01

    Microrheology, the study of the behavior of fluids on the microscopic scale, has been and continues to be one of the most important subjects that can be applied to characterize the behavior of biological fluids. It is extremely difficult to make rapid measurement of the viscoelastic properties of the interior of living cells. Liposomes are widely used as model system for studying different aspects of cell biology. We propose to develop a microrheometer, based on real-time control of optical tweezers, in order to investigate the viscoelastic properties of the fluid inside liposomes. This will give greater understanding of the viscoelastic properties of the fluids inside cells. In our experiment, the liposomes are prepared by different methods to find out both a better way to make GUVs and achieve efficient encapsulation of particle. By rotating the vaterite inside a liposome via spin angular momentum, the optical torque can be measured by measuring the change of polarization of the transmitted light, which allows the direct measurement of viscous drag torque since the optical torque is balanced by the viscous drag. We present an initial feasibility demonstration of trapping and manipulation of a microscopic vaterite inside the liposome. The applied method is simple and can be extended to sensing within the living cells.

  3. Nocturnal Hypoglycemia: Answering the Challenge With Long-acting Insulin Analogs

    PubMed Central

    Brunton, Stephen A.

    2007-01-01

    Background Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases. Objectives The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin. Data Sources A total of 307 publications (151 PubMed; 104 Adis; 52 BIOSIS) were reviewed. Review Methods Relevant trials were found by searching for “(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes.” To capture trials that may not have specified “nocturnal” in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using “(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes” was undertaken. Results A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs (insulin detemir or insulin glargine), provided that glycemic control is comparable to that provided by traditional human basal insulin. Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion. Conclusions Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control. PMID:17955093

  4. Long-acting muscarinic antagonists: a potential add-on therapy in the treatment of asthma?

    PubMed

    Busse, William W; Dahl, Ronald; Jenkins, Christine; Cruz, Alvaro A

    2016-03-01

    Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities. PMID:26929422

  5. Risks versus benefits of different types of long-acting injectable antipsychotics.

    PubMed

    McEvoy, Joseph P

    2006-01-01

    Since their introduction into clinical practice in the early 1960s, long-acting depot antipsychotics have been widely used as maintenance therapy for patients with schizophrenia. The improved pharmacokinetics of injectable long-acting antipsychotic therapies have provided more reliable drug delivery and reduced differences in peak and trough plasma levels of the drug. Studies that have compared short-acting oral antipsychotics with long-acting injectable antipsychotics, although imperfect, support injectable antipsychotics as having real benefit over oral antipsychotics on patient outcome owing largely to improved adherence. If patients forget or refuse to take their prescribed oral medications, weeks or months may go by before they experience an exacerbation; the effects of nonadherence become apparent too late to preempt the problem. On the other hand, if a patient fails to show up for an injection, the problem of nonadherence can be immediately addressed. When injectable medication is combined with an active psychosocial treatment program that will respond assertively to nonadherence, relapse rates may be reduced. By preventing or delaying relapse, consistent treatment can improve the patient's quality of life and lead to an overall reduction in the cost of care. PMID:16822092

  6. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy.

    PubMed

    Alphs, Larry; Nasrallah, Henry A; Bossie, Cynthia A; Fu, Dong-Jing; Gopal, Srihari; Hough, David; Turkoz, Ibrahim

    2016-07-01

    Many patients with schizophrenia will relapse despite uninterrupted antipsychotic (AP) long-acting therapy (LAT). This exploratory analysis examined variables associated with relapse despite ensured adherence to LAT. This was a post-hoc exploratory analysis of a 1-year study of risperidone long-acting injection in patients with stable schizophrenia or schizoaffective disorder (NCT00297388; N=323). Patients were discontinued from previous oral APs and randomly assigned to biweekly intramuscular injections of risperidone long-acting injectable 50 (n=163) or 25 mg (n=161) for 52 weeks. Cox proportional hazards regression models examined variables putatively associated with relapse. A total of 59/323 (18.3%) patients relapsed over 12 months despite continuous AP LAT. Variables associated with the risk of relapse included illness duration (6.0% increase each year; P=0.0003) and country (Canada vs. USA, 4.7-fold risk increase; P=0.0008). When illness duration was further categorized as ≤5, 6-10, and >10 years, patients with an illness duration of >10 versus ≤5 years were at greatest risk of relapse (>10 vs. ≤5 years associated with a 4.4-fold increase in the risk of relapse; P=0.0181). Findings suggest that patients with more chronic illness have a greater risk of relapse despite ensured treatment adherence, supporting the need for early intervention to prevent the deleterious effects of chronicity. PMID:26974214

  7. Intrathecal morphine for post-thoracotomy pain.

    PubMed

    Gray, J R; Fromme, G A; Nauss, L A; Wang, J K; Ilstrup, D M

    1986-08-01

    We wished to investigate possible differences in the duration of postoperative analgesia and the incidence of respiratory depression after the intrathecal injection in the lumbar area of 10 micrograms/kg morphine in hypobaric and hyperbaric solution for relief of post-thoracotomy pain. Twenty-nine patients received morphine plus dextrose (hyperbaric) and 21 received morphine in preservative-free normal saline. The duration of analgesia was longer with the morphine in the normal saline group than in the hyperbaric group (P less than 0.04). One patient developed delayed respiratory depression. Our data support the use of morphine in normal saline mixtures for greater duration of analgesia after thoracic operations. PMID:3755305

  8. The radiation dosimetry of intrathecally administered radionuclides

    SciTech Connect

    Stabin, M.G.; Evans, J.F.

    1999-01-01

    The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energy deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.

  9. Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability

    PubMed Central

    Singh, Sourabh Moti; Haddad, Peter M.; Husain, Nusrat; Heaney, Eamonn; Tomenson, Barbara; Chaudhry, Imran B.

    2016-01-01

    Objectives: The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). Method: A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. Results: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Conclusions: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including

  10. Prevention of unintended pregnancy: a focus on long-acting reversible contraception.

    PubMed

    Pickle, Sarah; Wu, Justine; Burbank-Schmitt, Edith

    2014-06-01

    This article summarizes the literature regarding the epidemiology and prevention of unintended pregnancy in the United States. Because of the Affordable Care Act and its accompanying contraceptive provision, there is a need for more primary care clinicians to provide family planning services. Office-based interventions to incorporate family planning services in primary care are presented, including clinical tools and electronic health record use. Special attention is paid to long-acting reversible contraceptive methods (the subdermal implant and intrauterine devices); these highly effective and safe methods have the greatest potential to decrease the rate of unintended pregnancy, but have been underused. PMID:24830607

  11. Increasing Use of Long-Acting Reversible Contraception to Decrease Unplanned Pregnancy.

    PubMed

    Lotke, Pamela S

    2015-12-01

    Unintended pregnancy remains high in the United States, accounting for one-half of pregnancies. Both contraceptive nonuse and imperfect use contribute to unplanned pregnancies. Long-acting reversible contraception (LARC) have greater efficacy than shorter acting methods. Data from large studies show that unplanned pregnancy rates are lower among women using LARC. However, overall use of LARC is low; of the reproductive age women using contraception, less than 10% are LARC users. Barriers include lack of knowledge and high up-front cost, and prevent more widespread use. Overcoming these barriers and increasing the number of women using LARC will decrease unplanned pregnancies and abortions. PMID:26598299

  12. [Guidelines on long-acting injectable atypical antipsychotics for first-episode schizophrenia].

    PubMed

    Azorin, J-M

    2013-09-01

    The current review raises the question of the place of long-acting injectable (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in current and future guidelines. After exposing the different points of view adopted in the former, the author presents the clinical trials conducted with LAI atypicals in this indication, as well as the surveys related to psychiatrists'opinion regarding the use of these drugs in early schizophrenia. Pros and cons of this therapeutic option are discussed and suggestions are made for further guidelines. PMID:24084422

  13. The Contraceptive CHOICE Project: Reducing Barriers to Long-Acting Reversible Contraception

    PubMed Central

    Secura, Gina M.; Allsworth, Jenifer E.; Madden, Tessa; Mullersman, Jennifer L.; Peipert, Jeffrey F.

    2010-01-01

    OBJECTIVE To introduce and promote the use of long-acting reversible methods of contraception (LARC; intrauterine contraceptives and subdermal implant) by removing financial and knowledge barriers. STUDY DESIGN The Contraceptive CHOICE Project is a prospective cohort study of 10,000 women 14-45 years who want to avoid pregnancy for at least one year and are initiating a new form of reversible contraception. Women screened for this study are read a script regarding LARC to increase awareness of these options. Participants choose their contraceptive method that is provided at no cost. We report the contraceptive choice and baseline characteristics of the first 2,500 women enrolled August 2007 through December 2008. RESULTS Sixty-seven percent of women enrolled (95% confidence interval: 65.3, 69.0) chose long-acting methods. Fifty-six percent selected intrauterine contraception and 11% selected the subdermal implant. CONCLUSION Once financial barriers were removed and LARC methods were introduced to all potential participants as a first-line contraceptive option, two-thirds chose LARC. PMID:20541171

  14. Acceptance of long-acting reversible contraceptive methods by adolescent participants in the Contraceptive CHOICE Project

    PubMed Central

    Mestad, Renee; Secura, Gina; Allsworth, Jenifer E; Madden, Tessa; Zhao, Qiuhong; Peipert, Jeffrey F

    2012-01-01

    Background Adolescent women have a high risk of unintended pregnancy. Currently, there are little data about their choice to initiate long-acting reversible contraception (LARC). Study Design We evaluated the association of age and preference for a LARC vs. a non-LARC method among adolescent participants in the Contraceptive CHOICE Project, comparing those aged 14–17 years to adolescents aged 18–20 years. We then analyzed the association between age and choice of the implant vs. the intrauterine device (IUD) among adolescents. Results Of the 5086 women enrolled, 70% (n=3557) of participants chose a LARC method. Among adolescents aged 14–20 years, 69% of 14–17-year-olds chose LARC, while 61% of 18–20-year-olds chose LARC (relative risk 1.16, 95% confidence interval 1.03–1.30). Among adolescents choosing a LARC method, 63% (n=93/148) of the 14–17-year-olds chose the implant, whereas 71% (n=364/510) of the 18–20-year-olds chose the IUD. Conclusion Long-acting reversible contraception use is clearly acceptable and common among adolescents enrolled in the Contraceptive CHOICE Project, with the younger group being most interested in the implant. PMID:22018123

  15. Cost and carbon burden of long-acting injections: a sustainable evaluation.

    PubMed

    Maughan, Daniel L; Lillywhite, Rob; Cooke, Matthew

    2016-06-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment - 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication - 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  16. Cost and carbon burden of long-acting injections: a sustainable evaluation

    PubMed Central

    Maughan, Daniel L.; Lillywhite, Rob; Cooke, Matthew

    2016-01-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment – 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication – 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  17. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  18. A Systemic Review and Experts' Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder.

    PubMed

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-08-31

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  19. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    PubMed Central

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-01-01

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  20. Risperidone long-acting injection: a review of its long term safety and efficacy

    PubMed Central

    Rainer, Michael K

    2008-01-01

    A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data) that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low. PMID:19183782

  1. Long-acting medications for the hyperkinetic disorders. A note on cost-effectiveness.

    PubMed

    Schlander, Michael

    2007-10-01

    New long-acting medications for attention-deficit/ hyperactivity disorder (ADHD) have become available, which combine certain advantages over conventional short-acting drugs with higher acquisition costs. Choices between these drugs should thus be driven by their clinical profiles and by an acceptable balance of increased costs and additional benefits. Accordingly, the notion of relative cost-effectiveness should be central to recommendations about the use of these drugs in practice. A recent technology assessment on behalf of the National Institute for Health and Clinical Excellence (NICE) did not identify differences between compounds in terms of clinical efficacy and described drug cost as the major driver of cost-effectiveness. The underlying economic model was restricted to a cost-utility analysis that used only a fraction of the available clinical evidence base and did not address the distinction between efficacy and effectiveness. Cost-effectiveness evaluations including the potential impact of improved treatment compliance indicate a relatively more attractive cost-effectiveness of long-acting medications than suggested by the NICE assessment. These evaluations provide health economic support to treatment recommendations recently published by the European Network for Hyperkinetic Disorders. Limitations of currently available economic evaluations include their short time horizon, and future research should assess treatment effects on long-term sequelae associated with ADHD. PMID:17401606

  2. Liposomes: Technologies and Analytical Applications

    NASA Astrophysics Data System (ADS)

    Jesorka, Aldo; Orwar, Owe

    2008-07-01

    Liposomes are structurally and functionally some of the most versatile supramolecular assemblies in existence. Since the beginning of active research on lipid vesicles in 1965, the field has progressed enormously and applications are well established in several areas, such as drug and gene delivery. In the analytical sciences, liposomes serve a dual purpose: Either they are analytes, typically in quality-assessment procedures of liposome preparations, or they are functional components in a variety of new analytical systems. Liposome immunoassays, for example, benefit greatly from the amplification provided by encapsulated markers, and nanotube-interconnected liposome networks have emerged as ultrasmall-scale analytical devices. This review provides information about new developments in some of the most actively researched liposome-related topics.

  3. Liposomal cytarabine (DepoCyte) for the treatment of neoplastic meningitis.

    PubMed

    Rueda Domínguez, Antonio; Olmos Hidalgo, David; Viciana Garrido, Ruth; Torres Sánchez, Esperanza

    2005-07-01

    Neoplastic meningitis is a feared complication in cancer patients, the median survival ranging from some weeks to a few months. Management is palliative and aims to provide symptoms relief while delaying neurological deterioration. Intrathecal methotrexate and/or cytarabine is the most widely used treatment in such clinical situations. These drugs are administered 2 or 3 times a week--a circumstance that is both bothersome for the patient and time-costly for the medical personnel. Liposomal cytarabine is a sustained-release cytarabine formulation specifically developed for the treatment of neoplastic meningitis. Its administration on a twice-weekly basis ensures sustained cytotoxic drug concentrations in cerebrospinal fluid. Controlled clinical trials have shown liposomal cytarabine to be equally or more effective than the classical treatment for neoplastic meningitis. In lymphomatous meningitis, liposomal cytarabine offers superior response rates, improved patient quality of life, and a prolongation of the time to neurological progression. When the cause of meningitis is a solid tumor, liposomal cytarabine prolongs the time to neurological progression and improves quality of life. These observations indicate that DepoCyte is a convenient treatment for patients with neoplastic meningitis, due to its efficacy and easy of administration characteristics. PMID:16131445

  4. Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

    PubMed

    Serata, Daniele; Rapinesi, Chiara; Kotzalidis, Georgios Demetrios; Alessi, Maria Chiara; Janiri, Delfina; Massolo, Anna Claudia; Ferri, Vittoria Rachele; Criscuolo, Silvia; Callovini, Gemma; Angeletti, Gloria; Girardi, Paolo; Del Casale, Antonio

    2015-01-01

    A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome. PMID:26443711

  5. Boronated liposome development and evaluation

    SciTech Connect

    Hawthorne, M.F.

    1995-11-01

    The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues.

  6. Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial.

    PubMed

    Gilmartin, R; Bruce, D; Storrs, B B; Abbott, R; Krach, L; Ward, J; Bloom, K; Brooks, W H; Johnson, D L; Madsen, J R; McLaughlin, J F; Nadell, J

    2000-02-01

    Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable. PMID:10695888

  7. Transformation pathways of liposomes.

    PubMed

    Hotani, H

    1984-09-01

    Liposomes undergoing transformation were observed by dark-field light microscopy in order to study the role of lipid in morphogenesis of biological vesicular structures. Liposomes were found to transform sequentially in a well-defined manner through one of several transformation pathways. A circular biconcave form was an initial shape in all the pathways and it transformed into a stable thin flexible filament or small spheres via a variety of regularly shaped vesicles which possessed geometrical symmetry. The transformation was reversible up to a certain point in each pathway. Osmotic pressure was found to be the driving force for the transformations. Biological membrane vesicles such as trypsinized red cell ghosts also transformed by similar pathways. PMID:6548263

  8. Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder.

    PubMed

    Lindenmayer, Jean-Pierre; Khan, Akbar; Eerdekens, Mariëlle; Van Hove, Ilse; Kushner, Stuart

    2007-01-15

    Subjects were patients with schizophrenia or schizoaffective disorder enrolled in extension studies (Study A and Study B) after participating in 12-week studies of long-acting injectable risperidone [Kane, J.M., Eerdekens, M., Lindenmayer, J.-P., Keith, S.J., Lesem, M., Karcher, K., 2003. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am. J. Psychiatry 160, 1125-1132; Lindenmayer, J.-P., Eerdekens, L., Berry, S., Eerdekens, M., 2004. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J. Clin. Psychiatry 65, 1084-1089]. Twelve months of treatment were completed by 55% of Study A patients and 52% of Study B patients. The median modal dose of long-acting injectable risperidone was 50 mg/14 days in both studies. Most frequent adverse events were psychosis, headache, insomnia, agitation, and rhinitis. EPS-related adverse events were reported in 33% of patients in Study A and 22% in Study B. Patients with Clinical Global Impressions ratings of "not ill" and "mild" increased from 14% at baseline to 54% at endpoint in Study A and from 42% to 65% in Study B. It is concluded that treatment with long-acting injectable risperidone for 1 year or longer appeared to be safe and well tolerated in patients with schizophrenia or schizoaffective disorder. PMID:17049818

  9. Liposomes for HIV prophylaxis

    PubMed Central

    Malavia, Nikita; Zurakowski, David; Schroeder, Avi; Princiotto, Amy; Laury, Anna Ray; Epstein-Barash, Hila; Sodroski, Joseph; Langer, Robert; Madani, Navid; Kohane, Daniel S.

    2012-01-01

    There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intravaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intravaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women. PMID:21862123

  10. Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide, Retrospective Inception Cohort Study

    PubMed Central

    Nielsen, Jimmi; Jensen, Signe O. W.; Friis, Rasmus B.; Valentin, Jan B.; Correll, Christoph U.

    2015-01-01

    Objective: To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). Methods: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician’s/patient’s choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Results: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87–1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86–1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86–1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78–1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. Conclusions: In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of

  11. Intrathecal synthesis of onconeural antibodies in patients with paraneoplastic syndromes.

    PubMed

    Corsini, Elena; Gaviani, Paola; Chiapparini, Luisa; Lazzaroni, Monica; Ciusani, Emilio; Bisogno, Raffaele; Silvani, Antonio; Salmaggi, Andrea; Bernardi, Gaetano

    2016-01-15

    Paraneoplastic neurological syndromes (PNSs) are a group of immune-mediated neurological disorders occurring in patients with systemic cancers which are associated with the presence of anti-neuronal antibodies. In this retrospective study, serum and cerebrospinal fluid of 489 patients were analyzed for the presence of well characterized onconeural antibodies. The 18 PNS patients positive for onconeural antibodies were reanalyzed to evaluate possible intrathecal synthesis. Intrathecal synthesis of onconeural antibodies, was detected in 10/15 patients affected by PNSs involving the CNS and in 1/3 cases with peripheral syndromes. Our data confirm that onconeural antibodies are produced within the CNS in most PNS patients. Evaluation of intrathecal synthesis of onconeural antibodies on a larger cohort of PNS patients and the correlation with disease course might elucidate whether this marker has a value in predicting the prognosis of the neurological disease. PMID:26711581

  12. Implantable Intrathecal Pumps for Chronic Pain: Highlights and Updates

    PubMed Central

    Knight, Karen H.; Brand, Frances M.; Mchaourab, Ali S.; Veneziano, Giorgio

    2007-01-01

    Management of chronic pain by intrathecal delivery is gaining increasing use. The aim of this article is to review the literature pertinent to implantable devices used for treatment of chronic pain, and to highlight what is known. Articles were obtained from Medline database and reviewed. Practical patient selection criteria, trial management, and surgical technique are described. Expert consensus guidelines for intrathecal medication use are also reviewed. Finally, an exhaustive description of known complications and future implications is discussed. We concluded that intrathecal pump seems to be overused, while there is still weak evidence to support its outcome. It is also recommended that future research focus on the outcome, measured by functional parameters rather than commonly used pain scores. PMID:17309136

  13. Effects of the protein corona on liposome-liposome and liposome-cell interactions.

    PubMed

    Corbo, Claudia; Molinaro, Roberto; Taraballi, Francesca; Toledano Furman, Naama E; Sherman, Michael B; Parodi, Alessandro; Salvatore, Francesco; Tasciotti, Ennio

    2016-01-01

    A thorough understanding of interactions occurring at the interface between nanocarriers and biological systems is crucial to predict and interpret their biodistribution, targeting, and efficacy, and thus design more effective drug delivery systems. Upon intravenous injection, nanoparticles are coated by a protein corona (PC). This confers a new biological identity on the particles that largely determines their biological fate. Liposomes have great pharmaceutical versatility, so, as proof of concept, their PC has recently been implicated in the mechanism and efficiency of their internalization into the cell. In an attempt to better understand the interactions between nanocarriers and biological systems, we analyzed the plasma proteins adsorbed on the surface of multicomponent liposomes. Specifically, we analyzed the physical properties and ultrastructure of liposome/PC complexes and the aggregation process that occurs when liposomes are dispersed in plasma. The results of combined confocal microscopy and flow cytometry experiments demonstrated that the PC favors liposome internalization by both macrophages and tumor cells. This work provides insights into the effects of the PC on liposomes' physical properties and, consequently, liposome-liposome and liposome-cell interactions. PMID:27445473

  14. Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus

    PubMed Central

    Andrews, Chasity D.; Spreen, William R.; Mohri, Hiroshi; Moss, Lee; Ford, Susan; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Bohm, Rudolf P.; Cheng-Mayer, Cecilia; Hong, Zhi; Markowitz, Martin; Ho, David D.

    2015-01-01

    GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP). PMID:24594934

  15. Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study.

    PubMed

    Simon, P; Fermanian, J; Ginestet, D; Goujet, M A; Péron-Magnan, P

    1978-07-01

    The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance. PMID:28102

  16. Committee Opinion No. 670 Summary: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454730

  17. Committee Opinion No. 670: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454734

  18. Long-Acting Muscarinic Antagonists for Difficult-to-Treat Asthma: Emerging Evidence and Future Directions.

    PubMed

    Bulkhi, Adeeb; Tabatabaian, Farnaz; Casale, Thomas B

    2016-07-01

    Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease. PMID:27289376

  19. Shared Decision Aids: Increasing Patient Acceptance of Long-Acting Reversible Contraception

    PubMed Central

    George, Tracy P.; DeCristofaro, Claire; Dumas, Bonnie P.; Murphy, Pamela F.

    2015-01-01

    Unintended pregnancies are an important public health issue. Long-acting reversible contraceptive methods (LARCs) are reliable, safe, highly effective methods for most women; however they are underutilized in the United States. Shared decision aids were added to usual care in five public health family planning clinics in the Southeastern United States, staffed by advance practice nurses and registered nurses. All five sites showed an increase in the use of LARCs during the time period that shared decision aids were used (results statistically significant to p < 0.001). It is important for women to make informed choices about contraception, and shared decision aids can be utilized to support this decision making. This resource has been adopted for statewide use in all public health clinics, and implications for practice suggest that the use of shared decision aids is an effective method to support informed patient decision making and acceptance of LARC methods of contraception. PMID:27417757

  20. Reversible Contraception Update: The Importance of Long-Acting Reversible Contraception

    PubMed Central

    Mestad, Renee E.; Kenerson, Jessica; Peipert, Jeffrey F.

    2011-01-01

    The past several years have seen an expansion in contraception options. Emerging data support the use of long-acting reversible contraception (LARC) such as the intrauterine device and subdermal implant as the most effective methods of contraception with the highest continuation rates and very high levels of patient satisfaction. In addition, the appropriate target population for the use of the intrauterine device now includes nulliparous women and adolescents. When a patient considers initiating a new contraceptive method, it is important to consider the characteristics of each method, including the side effects, effectiveness, and patient acceptability. Additionally, medical comorbidities must also be evaluated prior to choosing a method. In this article, we provide a brief overview of available reversible contraceptive methods, with an emphasis on LARC. PMID:19641264

  1. Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

    PubMed

    Melani, Andrea S; Sestini, Piersante

    2016-05-01

    Inhaled bronchodilators - such as long-acting muscarinic receptor antagonists (LAMAs) - are central to the pharmacological management of symptomatic chronic obstructive pulmonary disease. LAMAs are considered to be safe drugs at recommended dosages. In the present issue of the Journal safety of umeclidinium, a recently marketed LAMA, at twice the recommended dosage, has been evaluated with good results in a Japanese, COPD population. However, because muscarinic receptors are expressed not only in the lungs but also at the level of heart, digestive and urinary apparatus, the potential exists for LAMAs to cause adverse events related to stimulation of receptors in these organs. Head-to-head and post-marketing vigilance studies are required to determine the profile risk of these drugs, ultimately, and whether differences exist between currently available LAMAs. PMID:26789695

  2. Plasma corticosteroid levels in rats maintained on a long-acting naltrexone delivery system.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1978-04-01

    A long-acting delivery system for naltrexone has been described, which blocked the antinociceptive action of 10 mg kg-1 s.c. dose of morphine in rats for a period of 2 to 3 months. Male Wistar rats implanted s.c. with such a delivery system showed highly significant depression of plasma corticosteroid levels (40.2% in one week and 22.4 to 27.2% in 3 months) as compared to placebo pellet-implanted animals. Morphine-dependent male rats implanted with 75 mg morphine pellets showed a small (17.5%) but significant increase in plasma corticosteroid levels as compared to the placebo controls 72 hr. after pellet implantation. PMID:663407

  3. Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-Acting Opiate Administration

    PubMed Central

    Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

    2013-01-01

    Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure – in contrast to withdrawal from acute drug exposure – but rather is manifested as exaggerated fear in response to explicit threat cues. PMID:24076207

  4. [Long-acting injectable antipsychotics. Overview and advice for daily routine care].

    PubMed

    Köhler, S; Heinz, A; Sterzer, P

    2014-09-01

    Recent investigations have demonstrated a significant reduction of relapse and hospitalization rates associated with the use of long-acting injectable antipsychotics (LAIs) in the treatment of schizophrenia. There are only marginal differences in the effectiveness of different specific LAIs. Furthermore, LAIs are comparable to the oral equivalents with respect to effectiveness and side effects. The occurrence of extrapyramidal motor disorders (EPD) is less frequent in second generation (SG) LAIs than in first generation (FG) LAIs. Moreover, specific characteristics of some substances should be considered: In SG-LAIs immediate onset of action is only applicable for olanzapine and paliperidone and FG-LAIs should always be given as a test dose first to assure a general tolerance. All LAIs have a high variability of plasma levels which complicates the dose titration. Last but not least, current research concerning long-term consequences of continuous treatment with antipsychotics and the potentially poorer response to antipsychotics should be considered. PMID:24113854

  5. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    PubMed Central

    Montemagni, Cristiana; Frieri, Tiziana; Rocca, Paola

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs) combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL). Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other SGA-LAIs are still lacking. Lastly, some data on their use, especially in first-episode or recent-onset schizophrenia and in refractory or treatment-resistant schizophrenia, is available. PMID:27143893

  6. The long-acting β2-adrenoceptor agonist olodaterol attenuates pulmonary inflammation

    PubMed Central

    Wex, Eva; Kollak, Ines; Duechs, Matthias J; Naline, Emmanuel; Wollin, Lutz; Devillier, Philippe

    2015-01-01

    Background and Purpose β2-adrenoceptor agonists are widely used in the management of obstructive airway diseases. Besides their bronchodilatory effect, several studies suggest inhibitory effects on various aspects of inflammation. The aim of our study was to determine the efficacy of the long-acting β2-adrenoceptor agonist olodaterol to inhibit pulmonary inflammation and to elucidate mechanism(s) underlying its anti-inflammatory actions. Experimental Approach Olodaterol was tested in murine and guinea pig models of cigarette smoke- and LPS-induced lung inflammation. Furthermore, effects of olodaterol on the LPS-induced pro-inflammatory mediator release from human parenchymal explants, CD11b adhesion molecule expression on human granulocytes TNF-α release from human whole blood and on the IL-8-induced migration of human peripheral blood neutrophils were investigated. Key Results Olodaterol dose-dependently attenuated cell influx and pro-inflammatory mediator release in murine and guinea pig models of pulmonary inflammation. These anti-inflammatory effects were observed at doses relevant to their bronchodilatory efficacy. Mechanistically, olodaterol attenuated pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL-8-induced neutrophil transwell migration. Conclusions and Implications This is the first evidence for the anti-inflammatory efficacy of a β2-adrenoceptor agonist in models of lung inflammation induced by cigarette smoke. The long-acting β2-adrenoceptor agonist olodaterol attenuated pulmonary inflammation through mechanisms that are separate from direct inhibition of bronchoconstriction. Furthermore, the in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for 4 days. PMID:25824824

  7. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder

    PubMed Central

    Chue, Pierre; Chue, James

    2016-01-01

    Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55–3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI

  8. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – focus on olodaterol

    PubMed Central

    Matera, Maria Gabriella; Ora, Josuel; Cazzola, Mario

    2015-01-01

    Olodaterol (BI 1744 CL) is a novel, once-daily long-acting β2-agonist (LABA) designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 μg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy. PMID:26676161

  9. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder.

    PubMed

    Chue, Pierre; Chue, James

    2016-01-01

    Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55-3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI

  10. [A history of antipsychotic long-acting injections in the treatment of schizophrenia].

    PubMed

    Crocq, M-A

    2015-02-01

    From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors. PMID:25598520

  11. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD - focus on olodaterol.

    PubMed

    Matera, Maria Gabriella; Ora, Josuel; Cazzola, Mario

    2015-01-01

    Olodaterol (BI 1744 CL) is a novel, once-daily long-acting β2-agonist (LABA) designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 μg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides a convincing alternative for patients remaining symptomatic with olodaterol monotherapy. PMID:26676161

  12. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter. PMID:24188474

  13. Survival of rabid rabbits after intrathecal immunization.

    PubMed

    Kesdangsakonwut, Sawang; Sunden, Yuji; Aoshima, Keisuke; Iwaki, Yoshimi; Okumura, Masahiro; Sawa, Hirofumi; Umemura, Takashi

    2014-06-01

    Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4-8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8-12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11-18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies. PMID:24397792

  14. Survival of rabid rabbits after intrathecal immunization

    PubMed Central

    Kesdangsakonwut, Sawang; Sunden, Yuji; Aoshima, Keisuke; Iwaki, Yoshimi; Okumura, Masahiro; Sawa, Hirofumi; Umemura, Takashi

    2014-01-01

    Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4–8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8–12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11–18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies. PMID:24397792

  15. Scoliosis, spinal fusion, and intrathecal baclofen pump implantation.

    PubMed

    Scannell, Brian; Yaszay, Burt

    2015-02-01

    This article reviews the incidence, management, and complications of scoliosis in patients with cerebral palsy. Treatment of scoliosis in patients with cerebral palsy includes both nonoperative and operative management and often the decision to proceed with surgery is a multidisciplinary decision. Because of severe spasticity, many of these patients undergo intrathecal baclofen pump placement before, during, or after posterior spinal fusion. The complication rates can be high with intrathecal baclofen pump placement, but many patients can have significant benefit with this therapy. PMID:25479781

  16. Intrathecal pain pumps: indications, patient selection, techniques, and outcomes.

    PubMed

    Bolash, Robert; Mekhail, Nagy

    2014-10-01

    Intrathecal drug delivery represents an advanced modality for refractory chronic pain patients as well as intractable spasticity. This article reviews the advantages and indications for intrathecal therapy, as well as recommendations for proper patient selection using a multidisciplinary team to provide a global assessment of the impact of chronic pain on the patient's well-being. The goals and expectations of trialing are discussed alongside advantages and disadvantages of several trialing techniques. A discussion of outcomes is presented for patients with chronic pain due to both malignant and nonmalignant causes. PMID:25240660

  17. The use of combined spinal-epidural technique to compare intrathecal ziconotide and epidural opioids for trialing intrathecal drug delivery.

    PubMed

    Gulati, Amitabh; Loh, Jeffrey; Puttanniah, Vinay; Malhotra, Vivek

    2013-03-01

    SUMMARY Choosing the initial medications for intrathecal delivery is often confusing and not standardized. We describe a novel way for using a combined spinal-epidural technique to compare two first-line medications for intrathecal delivery; ziconotide and morphine (or hydromorphone). Five patients with intractable chronic or cancer pain were elected to have an intrathecal drug delivery system implanted for pain management. Each patient was given a 3-day inpatient trial with the combined spinal-epidural technique. The Visual Analog Scale, Numerical Rating Scale, short-term McGill questionnaire and opioid consumption were monitored daily. The results were used to develop a paradigm to describe how ziconotide can be used in practice. PMID:24645996

  18. Monodisperse Uni- and Multicompartment Liposomes.

    PubMed

    Deng, Nan-Nan; Yelleswarapu, Maaruthy; Huck, Wilhelm T S

    2016-06-22

    Liposomes are self-assembled phospholipid vesicles with great potential in fields ranging from targeted drug delivery to artificial cells. The formation of liposomes using microfluidic techniques has seen considerable progress, but the liposomes formation process itself has not been studied in great detail. As a result, high throughput, high-yielding routes to monodisperse liposomes with multiple compartments have not been demonstrated. Here, we report on a surfactant-assisted microfluidic route to uniform, single bilayer liposomes, ranging from 25 to 190 μm, and with or without multiple inner compartments. The key of our method is the precise control over the developing interfacial energies of complex W/O/W emulsion systems during liposome formation, which is achieved via an additional surfactant in the outer water phase. The liposomes consist of single bilayers, as demonstrated by nanopore formation experiments and confocal fluorescence microscopy, and they can act as compartments for cell-free gene expression. The microfluidic technique can be expanded to create liposomes with a multitude of coupled compartments, opening routes to networks of multistep microreactors. PMID:27243596

  19. Liposome: classification, preparation, and applications

    NASA Astrophysics Data System (ADS)

    Akbarzadeh, Abolfazl; Rezaei-Sadabady, Rogaie; Davaran, Soodabeh; Joo, Sang Woo; Zarghami, Nosratollah; Hanifehpour, Younes; Samiei, Mohammad; Kouhi, Mohammad; Nejati-Koshki, Kazem

    2013-02-01

    Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to `second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.

  20. Properties of liposomes containing 212Pb.

    PubMed

    Rosenow, M K; Zucchini, G L; Bridwell, P M; Stuart, F P; Friedman, A M

    1983-01-01

    The reverse phase evaporation method was used to prepare lipid bilayer membrane vesicles containing 212Pb and other markers of high specific activity. Electron microscopy and microfiltration were used to measure the sizes of the liposomes. Isotopes were released from the liposomes during exposure to serum and this leakage was prevented by complexing of small molecules with proteins or by precipitating particulate complexes within the liposomes. The in vivo distribution of 212Pb liposomes differed from the distribution of free 212Pb in that the reticuloendothelial system cleared the liposomes. Liposomes with surface dinitrophenol hapten were highly immunogenic and the humoral response to dinitrophenol was nonspecifically suppressed by 212Pb liposomes. PMID:6363323

  1. Migrating lumbar intrathecal catheter fragment associated with intracranial subarachnoid hemorrhage.

    PubMed

    Hnenny, Luke; Sabry, Hatem A; Raskin, Jeffrey S; Liu, Jesse J; Roundy, Neil E; Dogan, Aclan

    2015-01-01

    Intrathecal catheter placement into the lumbar cistern has varied indications, including drug delivery and CSF diversion. These Silastic catheters are elastic and durable; however, catheter-associated malfunctions are well reported in the literature. Fractured catheters are managed with some variability, but entirely intradural retained fragments are often managed conservatively with observation. The authors describe a case of a 70-year-old man with an implanted intrathecal morphine pump for failed back surgery syndrome who presented to an outside hospital with a history of headache, neck pain, nausea, and photophobia of 3 days' duration. He also described mild weakness and intermittent numbness of both legs. Unenhanced head CT demonstrated subarachnoid hemorrhage (SAH). A right C-5 hemilaminectomy was performed. This case is unique in that there was no indication that the lumbar intrathecal catheter had fractured prior to the patient's presentation with SAH. This case demonstrates that intrathecal catheter fragments are mobile and can precipitate intracranial morbidity. Extrication of known fragments is safe and should be attempted to prevent further neurosurgical morbidity. PMID:25360531

  2. Review of Intrathecal Baclofen Therapy for Spastic and Rigidity Disorders

    ERIC Educational Resources Information Center

    Obringer, S. John; Coffey, Kenneth M.

    2002-01-01

    Intrathecal baclofen therapy, a treatment for cerebral palsy and other spastic and rigidity disorders, is showing promise as an effective intervention. This article synthesizes both the medical and rehabilitation conceptual literature to update educators and related service providers as to the efficacy of this intervention. Implications for…

  3. Italian multicentre study on intrathecal fluorescein for craniosinusal fistulae

    PubMed Central

    Felisati, G; Bianchi, A; Lozza, P; Portaleone, S

    2008-01-01

    Summary Cerebrospinal fluid leak (CSF), clinical sign of a dural lesion of the skull base, is a relatively rare event that can present with a variety of symptoms. Every craniosinus fistula should be considered a serious, potentially life-threatening situation (even those cases with hidden CSF leak). Reports of experience concerning diagnosis and treatment of craniosinus fistulae have appeared in the Literature. In the last few years, the endoscopic nasal approach is proving effective as it makes diagnosis much easier and is the least invasive surgical approach, with the greatest percentage of success. Various classifications are being proposed to improve clinical evaluation of CSF leaks and to simplify the diagnostic and therapeutic approach. The most common parameters of classification are: aetiology (traumatic, iatrogenic, non-traumatic, etc.) site, type of flow (high or low pressure) and, as far as concerns treatment, the type of graft used, all of which have contributed to various diagnostic and therapeutic algorithms being proposed. Therefore, the subject seems to be widely schematized and the therapeutic attitude widely agreed. However, one of the diagnostic and therapeutic approaches is now being questioned. For some, it is the heart of the clinical approach, while for others, it is a useful tool yet too dangerous to be used on account of potential side effects: namely, the fluorescein test. This procedure, consisting of intrathecal injection of a colorant (fluorescein), is well known by the Food and Drug Administration (FDA) which neither explicitly prohibits it, nor allows it, intrathecal administration is, therefore. an off label use. As far as the Authors know, authorization of this procedure has not been forthcoming anywhere in the world although the procedure itself is widely employed. As far as concerns the use of intrathecal fluorescein, many scientific papers have been written, clearly supporting its clinical usefulness. One limit to the use of

  4. Combined corticosteroid and long-acting beta2-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease

    PubMed Central

    Nannini, Luis Javier; Lasserson, Toby J; Poole, Phillippa

    2014-01-01

    Background Both inhaled steroids (ICS) and long-acting beta2-agonists (LABA) are used in the management of chronic obstructive pulmonary disease (COPD). This updated review compared compound LABA plus ICS therapy (LABA/ICS) with the LABA component drug given alone. Objectives To assess the efficacy of ICS and LABA in a single inhaler with mono-component LABA alone in adults with COPD. Search methods We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search was November 2011. Selection criteria We included randomised, double-blind controlled trials. We included trials comparing compound ICS and LABA preparations with their component LABA preparations in people with COPD. Data collection and analysis Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, while secondary outcomes were health-related quality of life (measured by validated scales), lung function, withdrawals due to lack of efficacy, withdrawals due to adverse events and side-effects. Dichotomous data were analysed as random-effects model odds ratios or rate ratios with 95% confidence intervals (CIs), and continuous data as mean differences and 95% CIs. We rated the quality of evidence for exacerbations, mortality and pneumonia according to recommendations made by the GRADE working group. Main results Fourteen studies met the inclusion criteria, randomising 11,794 people with severe COPD. We looked at any LABA plus ICS inhaler (LABA/ICS) versus the same LABA component alone, and then we looked at the 10 studies which assessed fluticasone plus salmeterol (FPS) and the four studies assessing budesonide plus formoterol (BDF) separately. The studies were well-designed with low risk of bias for randomisation and blinding but they had high rates of attrition, which reduced our confidence in the results for outcomes other than mortality. Primary outcomes There was low quality

  5. “Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

    PubMed Central

    van den Berg, Jacob J.; Rosen, Rochelle K.; Bregman, Dana E.; Thompson, Lara A.; Jensen, Kathleen M.; Kiser, Patrick F.; Katz, David F.; Buckheit, Karen; Buckheit, Robert W.; Morrow, Kathleen M.

    2014-01-01

    Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use. PMID:24248674

  6. Liposome: classification, preparation, and applications

    PubMed Central

    2013-01-01

    Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to ‘second-generation liposomes’, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:23432972

  7. Permanent Sterilisation to Long-Acting Reversible Contraception: Is a Paradigm Shift Necessary?

    PubMed

    Shantha Kumari, S

    2016-06-01

    The concept of family planning originated as birth control in 1912 to control the size of the family and prevent unplanned pregnancies transformed to family welfare and later on expanded its horizons to reproductive and child health (RCH). A wide spectrum of choices both for male and female, temporary and permanent, have been developed and offered. Developed world having stabilised population faces problem with teenage and adolescent pregnancies. Developing nations are still struggling to stabilise population and traditionally depend on permanent female sterilisation as a major method of contraception. Lot of unmet need is seen in young recently married women, post-delivery, post-abortal states. Long-acting reversible contraception which includes intrauterine device, IUD, and implants has re-emerged strongly as a first choice of contraception for women of all ages including unmarried teenage pregnancies. They are highly efficient with failure rates equivalent or better than permanent methods, cost-effective, reversible, and have the potential to replace permanent sterilisation. PMID:27298522

  8. Planning ahead for implementation of long acting HIV prevention: challenges and opportunities

    PubMed Central

    Meyers, Kathrine

    2015-01-01

    Purpose of Review Broad-based access, uptake, and dissemination of daily oral HIV pre-exposure prophylaxis (PrEP) have been slow, despite strong evidence for efficacy. Effective and efficient implementation of long-acting (LA) HIV prevention products will require both analysis of the dynamics and determinants of daily oral PrEP implementation and identification of the distinct challenges and opportunities inherent in emerging technologies. Recent Findings Evidence suggests the importance of addressing implementation issues at three levels: patient, provider, and system. Patient-level factors include targeted education and messaging, tailored supports to enhance acceptability and uptake, and effective strategies for promoting adherence/persistence and retention in care. Provider-level factors include engaging a broad mix of providers, while ensuring adequate training and support for patient assessment, counseling, and follow-up. Systems-level factors include optimal delivery modalities, resource allocation, and ensuring access to populations most in need of new prevention options. Summary Formative social/behavioral research must be undertaken proactively in order to prepare for and address future implementation challenges and reduce the gap between proving efficacy in clinical trials and assuring real-world effectiveness. Conceptualizing new HIV prevention technologies as behavioral interventions at the level of the patient, provider, and system will be paramount to effective and efficient implementation. PMID:26049956

  9. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal.

  10. Pharmacokinetics and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats.

    PubMed

    Albarellos, G A; Montoya, L; Quaine, P C; Landoni, M F

    2011-08-01

    The pharmacokinetic profile and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats was investigated. Single intravenous (cephalexin lysine salt) and intramuscular (20% cephalexin monohydrate suspension) were administered to five cats at a dose rate of 10 mg/kg. Serum disposition curves were analyzed by noncompartmental approaches. After intravenous administration, volume of distribution (V(z)), total body clearance (Cl(t)), elimination constant (λ(z)), elimination half-life (t(½)(λ)) and mean residence time (MRT) were: 0.33±0.03 L/kg; 0.14±0.02 L/hkg, 0.42±0.05 h(-1), 1.68±0.20 h and 2.11±0.25 h, respectively. Peak serum concentration (C(max)), time to peak serum concentration (T(max)) and bioavailability after intramuscular administration were 15.67±1.95 μg/mL, 2.00±0.61 h and 83.33±8.74%, respectively. PMID:20800248

  11. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.

    PubMed

    Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

    2015-01-14

    Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women. PMID:25589631

  12. Treatment effectiveness and adherence in patients with schizophrenia treated with risperidone long-acting injection.

    PubMed

    Chang, Chen-Lin; Tzeng, Dong-Sheng; Lung, For-Wey

    2010-11-30

    This study investigated the variables related to the effectiveness and adherence to treatment with risperidone long-acting injection (RLAI) in patients with schizophrenia. We performed a retrospective medical chart review of 137 patients with schizophrenia who were prescribed RLAI between July 2004 and December 2006. Cox regression analysis showed that the effectiveness of treatment in patients treated with RLAI was affected significantly by the provision of home care and the use of illicit drugs. The adherence of patients to treatment with RLAI was affected most by the provision of home care. Bayesian analysis showed that patients who received the provision of home care or who had no history of illicit drug use continued treatment for, on average, 15.27 and 17.14days longer, respectively, than those who did not receive such care or take illicit drugs. Patients who received the provision of home care adhered to treatment for 343.98 more days than those who did not. Even though patients taking RLAI show better adherence than those taking oral risperidone, home care services can have a significant additional effect on adherence. Randomized clinical follow-up trial studies are necessary to explore the risk factors for nonadherence in more detail. PMID:20488552

  13. Plasma bioavailability of 2 long-acting oxytetracycline formulations in the pig.

    PubMed

    Archimbault, P; Navetat, H; Vidal, R; Douin, M J; Mignot, A

    1994-01-01

    Two commercially available long-acting oxytetracycline (OTC-LA) formulations were administered by intramuscular injection in 2 groups of 10 clinically healthy pigs at the recommended dose level of 20 mg/kg. Plasma concentrations were analysed by high-performance liquid chromatography (HPLC) of a period of 0 to 84 h. The limit of quantification of the assay was 0.125 microgram/ml. The comparison of the CMAX did not reveal any significant differences (4.45 +/- 1.30 and 4.40 +/- 0.9 micrograms/ml). The results were similar for the TMAX (3.60 +/- 1.58 and 4.00 +/- 2.67 h). The areas under the curve were also similar. The AUC0-84 h results were respectively 92.8 +/- 14.1 and 96.3 +/- 11.3 mg.h/l and the AUC0-infinity results were 99.5 +/- 14.7 and 106.7 +/- 15.4 mg.h/l. No significant difference was found. This may be considered as a preliminary study to demonstrate the bioequivalence of the 2 preparations. On the basis of the statistical analysis of the results obtained, a cross-over study using 2 groups of 20 animals is theoretically necessary for such a demonstration. PMID:8087147

  14. Demand for long-acting and permanent contraceptive methods among Kurdish women in Mahabad, Iran.

    PubMed

    Hosseini, Hatam; Torabi, Fatemeh; Bagi, Balal

    2014-11-01

    It is anticipated that the demand for contraceptives in Iran will increase in the near future as the number of women of reproductive age increases and with women wanting smaller families. The aim of this paper was to study the demand for long-acting and permanent contraceptive methods (LAPCMs), and its determinants, among Kurdish women in Mahabad city, Iran. Data were taken from the Mahabad Fertility Survey (MFS) conducted on a sample of over 700 households in April 2012. The results show that the demand for LAPCMs was 71.35% at the time of survey, although only 27.7% of women were using these methods. Thus, the number of unintended pregnancies is likely to increase in the future if this gap is not reduced. The multivariate analysis showed significant impacts on the dependent variables of the number of children ever born, perceived contraceptive costs and childbearing intentions. Moreover, women at the end of their reproductive lives and those with higher education were more likely to desire LAPCMs. It is concluded that despite a growing use of contraceptive methods in Iran in recent decades, the development of reproductive health services and promotion of the quality of family planning services remains a necessity. PMID:24406051

  15. Comparison of attitudes toward long-acting injectable antipsychotics among psychiatrists and patients.

    PubMed

    Kim, Sung-Wan; Lee, Yo-Han; Jang, Ji-Eun; Yoo, Taeyoung; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang

    2013-03-01

    The current prescription rate of long-acting injectable antipsychotics (LAI) is less than 1% in Korea. This study aimed to investigate the reason for LAI underuse by surveying the attitudes toward LAI among psychiatrists and patients receiving LAI. A total of 173 psychiatrists and 99 patients receiving LAI participated in the survey. Participating psychiatrists were divided into two groups according to experience with prescribing LAI to at least 10 patients. The two psychiatrist groups did not differ significantly in terms of sociodemographic characteristics and clinical practice patterns. However, the group with higher experience more frequently provided explanations of LAI to their patients and was more satisfied with the use of LAI than the group with less experience. Acceptance rates of patients to the recommendation for LAI treatment and satisfaction of psychiatrists with the outcome of LAI were also significantly higher in the group with higher experience. Psychiatrists with less experience with LAI were more negative toward LAI than patients receiving LAI as well as psychiatrists with higher experience. In conclusion, attitudes of psychiatrists toward LAI were closely related to the use of LAI. The negative attitude and reluctance of psychiatrists, rather than patient resistance, may contribute toward the underuse of LAI. PMID:23325306

  16. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    PubMed

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID:27253622

  17. Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

    PubMed

    Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

    2006-07-01

    A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

  18. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma

    PubMed Central

    Xia, Ying; Kelton, Christina M. L.; Xue, Liang; Bian, Boyang; Wigle, Patricia R.

    2013-01-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  19. Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.

    PubMed

    Loutradis, Dimitris; Drakakis, Petros; Vlismas, Antonis; Antsaklis, Aristidis

    2009-04-01

    Corifollitropin alfa is being developed by Schering-Plough Corp as an injectable, long-acting follicle-stimulating hormone (FSH) agonist for the treatment of infertility. A single dose of corifollitropin alfa could initiate and sustain multifollicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection. The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH. Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing. The drug was well tolerated and does not appear to be associated with any serious adverse events or the formation of antibodies. The initial results from a large, phase III, double-blind clinical trial indicated that the ongoing pregnancy rate achieved with corifollitropin alfa treatment was high and similar to the rate established with daily treatment of recombinant FSH. The number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment. Thus, corifollitropin alfa has the potential to serve as a viable fertility agent and to gain a place in the infertility market. PMID:19337959

  20. Eliminating health disparities in unintended pregnancy with long-acting reversible contraception (LARC).

    PubMed

    Parks, Caitlin; Peipert, Jeffrey F

    2016-06-01

    Significant public health disparities exist surrounding teen and unplanned pregnancy in the United States. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed, they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act and more widespread, no-cost coverage of methods, more and more women are choosing intrauterine devices and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the United States and improve women's and children's health. PMID:26875950

  1. Effectiveness of long-acting paliperidone palmitate in borderline personality disorder.

    PubMed

    Palomares, Nerea; Montes, Ana; Díaz-Marsá, Marina; Carrasco, José L

    2015-11-01

    The aim of the present study is to test the efficacy of palmitate paliperidone long-acting injection for patients with borderline personality disorder (BPD). A total of 16 patients with BPD were treated with intramuscular paliperidone palmitate (IMPP) over 12 weeks. Effectiveness measures included the CGI-BPD, HARS, MADRS, BIS-11, and STAXI-2. Functional improvement was assessed using the Global Assessment of Functioning scale. A list of adverse events was provided to clinicians and patients. Treatment with IMPP was associated with a significant average reduction of 1.6 (95% confidence interval: 1192-2008; P>0.01) in CGI-BPD scores and an average increase of psychosocial functioning as scored by the Global Assessment of Functioning scale of 13.3 (95% confidence interval: 8.35-18.31; P>0.01) was obtained. The treatment decreased impulsive-disruptive behaviors and improved general functioning. An acceptable tolerance was observed. The average weight gain was clinically irrelevant despite being statistically significant. No other relevant adverse side effects were reported, with the exception of galactorrhea, which required suspension of treatment in three patients. IMPP seems to be a well-tolerated alternative to other second-generation antipsychotics in the treatment of BPD. More controlled studies replicating these results should be proposed in the future. PMID:26230268

  2. Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia.

    PubMed

    Di Lorenzo, Rosaria; Brogli, Alice

    2010-01-01

    Olanzapine long-acting injection (OLAI) is a crystalline salt composed of olanzapine and pamoic acid, which permits a depot intramuscular formulation of olanzapine. The half-life of olanzapine pamoate is 30 days, and its steady state is reached approximately at 12 weeks. Oral supplementation of olanzapine is not required during OLAI initiation, according to Eli Lilly recommendations, although a study indicated that ≥60% of D(2) receptor occupancy was reached only by the fifth injection cycle. To date, a short-term, placebo-controlled study of 8 weeks in acutely ill patients and a long-term, controlled trial of 24 weeks in stabilized patients have been conducted. In both the studies, efficacy and safety were similar to those of oral olanzapine, with the exception of an acute adverse effect, the so-called inadvertent intravascular injection event, which occurred 1-3 hours after the injection with an incidence rate of 0.07% per injection. It consisted of symptoms that are similar to those reported in cases of oral olanzapine overdose. The most significant studies published to date, on the use of olanzapine pamoate in schizophrenia, are reviewed in this article. The pharmacodynamic and pharmacokinetic profile and related side effects of OLAI are reported. PMID:20856920

  3. Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia

    PubMed Central

    Di Lorenzo, Rosaria; Brogli, Alice

    2010-01-01

    Olanzapine long-acting injection (OLAI) is a crystalline salt composed of olanzapine and pamoic acid, which permits a depot intramuscular formulation of olanzapine. The half-life of olanzapine pamoate is 30 days, and its steady state is reached approximately at 12 weeks. Oral supplementation of olanzapine is not required during OLAI initiation, according to Eli Lilly recommendations, although a study indicated that ≥60% of D2 receptor occupancy was reached only by the fifth injection cycle. To date, a short-term, placebo-controlled study of 8 weeks in acutely ill patients and a long-term, controlled trial of 24 weeks in stabilized patients have been conducted. In both the studies, efficacy and safety were similar to those of oral olanzapine, with the exception of an acute adverse effect, the so-called inadvertent intravascular injection event, which occurred 1–3 hours after the injection with an incidence rate of 0.07% per injection. It consisted of symptoms that are similar to those reported in cases of oral olanzapine overdose. The most significant studies published to date, on the use of olanzapine pamoate in schizophrenia, are reviewed in this article. The pharmacodynamic and pharmacokinetic profile and related side effects of OLAI are reported. PMID:20856920

  4. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  5. Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application.

    PubMed

    Kesteleyn, Bart; Amssoms, Katie; Schepens, Wim; Hache, Geerwin; Verschueren, Wim; Van De Vreken, Wim; Rombauts, Klara; Meurs, Greet; Sterkens, Patrick; Stoops, Bart; Baert, Lieven; Austin, Nigel; Wegner, Jörg; Masungi, Chantal; Dierynck, Inge; Lundgren, Stina; Jönsson, Daniel; Parkes, Kevin; Kalayanov, Genadiy; Wallberg, Hans; Rosenquist, Asa; Samuelsson, Bertil; Van Emelen, Kristof; Thuring, Jan Willem

    2013-01-01

    The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R(3)) at the para-position of the P1' benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R(1)) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC(50)s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS. PMID:23177258

  6. Global trends in use of long-acting reversible and permanent methods of contraception: Seeking a balance.

    PubMed

    Joshi, Ritu; Khadilkar, Suvarna; Patel, Madhuri

    2015-10-01

    The global trend shows that the use of permanent contraception to prevent unintended pregnancy is high. Although the trend also shows a rise in the use of long-acting reversible methods, these are still underutilized despite having contraceptive as well as non-contraceptive benefits. Lack of knowledge among women, dependence on the provider for information, and provider bias for permanent contraception are cited as reasons for this reduced uptake. Training of healthcare providers and increased patient awareness about the effectiveness of long-acting reversible contraceptive methods will increase their uptake and help prevent unintended pregnancies. PMID:26433510

  7. Liposome Technology for Industrial Purposes

    PubMed Central

    Wagner, Andreas; Vorauer-Uhl, Karola

    2011-01-01

    Liposomes, spherical vesicles consisting of one or more phospholipid bilayers, were first described in the mid 60s by Bangham and coworkers. Since then, liposomes have made their way to the market. Today, numerous lab scale but only a few large-scale techniques are available. However, a lot of these methods have serious limitations in terms of entrapment of sensitive molecules due to their exposure to mechanical and/or chemical stress. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability. An additional point of view was taken to regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:21490754

  8. ROLE OF MENINGEAL MAST CELLS IN INTRATHECAL MORPHINE EVOKED GRANULOMA FORMATION

    PubMed Central

    Yaksh, Tony L.; Allen, Jeffery W.; Veesart, Samantha L.; Horais, Kjersti A; Malkmus, Shelle A.; Scadeng, Miriam; Steinauer, Joanne J.; Rossi, Steve S

    2013-01-01

    Background Intrathecal morphine forms granulomas that arise from the adjacent arachnoid membrane. We propose that these inflammatory cells exit the meningeal vasculature secondary to meningeal mast cell degranulation. Methods Three sets of experiments were accomplished in dogs. 1) Ex vivo Meningeal mast cell degranulation. Histamine release was measured ex vivo from canine dura incubated with opiates. 2) In vivo cutaneous mast cell degranulation. Flare areas on the dog abdomen were measured after subcutaneous opiates. 3) In vivo granuloma pharmacology. Dogs with lumbar intrathecal catheters received infusion of intrathecal saline or intrathecal morphine. Intrathecal morphine dogs received: i) No other treatment (Control); ii) Twice daily subcutaneous naltrexone; iii) Intrathecal co-infusion of cromolyn; or, iv) Twice daily subcutaneous cromolyn for the 24–28 day study course. Results 1) Morphine but not fentanyl evoked dural histamine release, which was blocked by cromolyn but not naloxone. 2) Wheal/flare was produced by subcutaneous morphine, methadone, hydromorphone, but not fentanyl, and was unaffected by naltrexone but prevented by cromolyn. 3) Granulomas occurred in all dogs receiving intrathecal morphine (15/15); subcutaneous naltrexone had no effect on granulomas (6/6), but was reduced by concurrent intrathecal cromolyn (0/5) or twice daily subcutaneous cromolyn (1 of 5). Conclusions The pharmacology of cutaneous/dural MC degranulation and intrathecal granulomas are comparable, not mediated by opioid receptors, and reduced by agents preventing MC degranulation. If an agent produces cutaneous MC degranulation at concentrations produced by intrathecal delivery, the agent may initiate granulomas. PMID:23426209

  9. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  10. 99m tc labeled liposomes

    SciTech Connect

    Phillips, W.T.; Klipper, R.W.; Timmons, J.H.; Rudolph, A.S.

    1992-10-27

    This patent describes a method of preparing stable gamma-emitting radionuclide-labeled alkyleneamine oxime, the incubating being for a period of time sufficient to form labeled liposome-encapsulated protein.

  11. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.

    PubMed

    Ersland, Kari M; Skrede, Silje; Røst, Therese H; Berge, Rolf K; Steen, Vidar M

    2015-12-01

    Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. PMID:26378122

  12. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  13. Long-acting Neuraminidase Inhibitor Laninamivir Octanoate as Post-exposure Prophylaxis for Influenza

    PubMed Central

    Kashiwagi, Seizaburo; Watanabe, Akira; Ikematsu, Hideyuki; Uemori, Mitsutoshi; Awamura, Shinichiro

    2016-01-01

    Background. A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, has been proven to be effective in the treatment of influenza but not for post-exposure prophylaxis. Methods. We conducted a double-blind, multicenter, randomized, placebo-controlled study to determine if a single administration of laninamivir octanoate 40 mg was superior to placebo for post-exposure prophylaxis. Eligible participants who had cohabited with an influenza patient within 48 hours of symptom onset were randomly assigned (1:1:1) to 1 of 3 groups: 40 mg of laninamivir octanoate single administration (LO-40SD), 20 mg of laninamivir octanoate once daily for 2 days (LO-20TD), or placebo. The primary efficacy endpoint was the proportion of participants who developed clinical influenza (defined as influenza virus positive, an axillary temperature >37.5°C, and at least 2 symptoms) over a 10-day period. Results. A total of 803 participants were enrolled, with 801 included in the primary analysis. The proportions of participants with clinical influenza were 4.5% (12/267), 4.5% (13/269), and 12.1% (32/265) in the LO-40SD, LO-20TD, and placebo groups, respectively. A single administration of laninamivir octanoate 40 mg significantly reduced the development of influenza compared with placebo (P = .001). The relative risk reductions compared with the placebo group were 62.8% and 63.1% for the LO-40SD and LO-20TD groups, respectively. The incidence of adverse events in the LO-40SD group was similar to that of the LO-20TD and placebo groups. Conclusions. A single administration of laninamivir octanoate was effective and well tolerated as post-exposure prophylaxis to prevent the development of influenza. Clinical Trials Registration. JapicCTI-142679. PMID:27118785

  14. Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

    PubMed Central

    Izquierdo, José Luis; Paredero, José Manuel; Piedra, Raul

    2016-01-01

    Introduction The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. Methods We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. Results During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. Conclusion The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. PMID:26929614

  15. Long-acting muscarinic antagonists for the prevention of exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Jones, Paul W

    2015-06-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) have important consequences for lung function, health status and mortality. Furthermore, they are associated with high economic costs, predominantly related to hospitalization. They are managed acutely with short-acting bronchodilators, systemic corticosteroids or antibiotics; however, a large proportion of COPD exacerbations are unreported and therefore untreated or self-managed. There is evidence to suggest that these unreported exacerbations also have important consequences for health status; therefore, reducing exacerbation risk is an important goal in the management of COPD. Current guidelines recommend long-acting muscarinic antagonists (LAMAs) as first-line bronchodilator therapy in patients with stable COPD who have a high risk of exacerbation or increased symptoms. To date, three LAMAs, tiotropium bromide, aclidinium bromide and glycopyrronium bromide, have been approved as maintenance bronchodilator treatments for stable COPD. These all provide clinically significant improvements in lung function, reduce symptoms and improve health status compared with placebo in patients with COPD. This paper reviews evidence from randomized, controlled clinical trials demonstrating that tiotropium, aclidinium and glycopyrronium reduce exacerbation risk in patients with COPD. Reductions were seen irrespective of the exacerbation measure used, whether time to first event or annualized exacerbation rate. Furthermore, studies with aclidinium suggest LAMAs can reduce exacerbation risk irrespective of whether exacerbation events are assessed, using an event-based approach or a symptom-based method which includes unreported events. Together these results demonstrate that LAMAs have the potential to provide clinical benefit in the management of exacerbations in patients with stable COPD. PMID:25801643

  16. Knowledge and attitudes about long-acting reversible contraception among Latina women who desire sterilization

    PubMed Central

    White, Kari; Hopkins, Kristine; Potter, Joseph E.; Grossman, Daniel

    2013-01-01

    Background There is growing interest in increasing the use of long-acting reversible contraception (LARC), and suggestions that such methods may serve as an alternative to sterilization. However, there is little information about whether women who do not want more children would be interested in using LARC methods. Methods We conducted semi-structured interviews with 120 parous Latina women in El Paso, Texas who wanted a sterilization but had not obtained one. We assessed women’s awareness of and interest in using the copper intrauterine device (IUD), levonorgestrel intrauterine system (LNG-IUS), and etonogestrel implant. Findings Overall, 51%, 23% and 47% of women reported they had heard of the copper IUD, LNG-IUS and implant, respectively. More women stated they would use the copper IUD (24%) than the LNG-IUS (14%) or implant (9%). Among women interested in LARC, the most common reasons were that, relative to their current method, LARC methods were more convenient, effective, and provided longer-term protection against pregnancy. Those who had reservations about LARC were primarily concerned with menstrual changes. Women also had concerns about side effects and the methods' effectiveness in preventing pregnancy, preferring to use a familiar method. Conclusions Although these findings indicate many Latina women in this setting do not consider LARC an alternative to sterilization, they point to an existing demand among some who wish to end childbearing. Efforts are needed to improve women’s knowledge and access to a range of methods so they can achieve their childbearing goals. PMID:23816156

  17. Systems Approach to targeted and long-acting HIV/AIDS therapy.

    PubMed

    Ho, Rodney J Y; Yu, Jesse; Li, Bowen; Kraft, John C; Freeling, Jennifer P; Koehn, Josefin; Shao, Jingwei

    2015-12-01

    Medication adherence and insufficient drug levels are central to HIV/AIDS disease progression. Recently, Fletcher et al. confirmed that HIV patients on oral antiretroviral therapy had lower intracellular drug concentrations in lymph nodes than in blood. For instance, in the same patient, multiple lymph node drug concentrations were as much as 99 % lower than in blood. This study built upon our previous finding that HIV patients taking oral indinavir had 3-fold lower mononuclear cell drug concentrations in lymph nodes than in blood. As a result, an association between insufficient lymph node drug concentrations in cells and persistent viral replication has now been validated. Lymph node cells, particularly CD4 T lymphocytes, host HIV infection and persistence; CD4 T cell depletion in blood correlates with AIDS progression. With established drug targets to overcome drug insufficiency in lymphoid cells and tissues, we have developed and employed a "Systems Approach" to engineer multi-drug-incorporated particles for HIV treatment. The goal is to improve lymphatic HIV drug exposure to eliminate HIV drug insufficiency and disease progression. We found that nano-particulate drugs that absorb, transit, and retain in the lymphatic system after subcutaneous dosing improve intracellular lymphatic drug exposure and overcome HIV lymphatic drug insufficiency. The composition, physical properties, and stability of the drug nanoparticles contribute to the prolonged and enhanced drug exposure in lymphoid cells and tissues. In addition to overcoming lymphatic drug insufficiency and potentially reversing HIV infection, targeted drug nanoparticle properties may extend drug concentrations and enable the development of long-acting HIV drug therapy for enhanced patient compliance. PMID:26315144

  18. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    PubMed Central

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients. PMID:24194642

  19. Long-acting reversible contraception: Findings from the Understanding Fertility Management in Contemporary Australia survey.

    PubMed

    Holton, Sara; Rowe, Heather; Kirkman, Maggie; Jordan, Lynne; McNamee, Kathy; Bayly, Chris; McBain, John; Sinnott, Vikki; Fisher, Jane

    2016-04-01

    Objectives The aim of this research was to investigate awareness, perceived reliability and consideration of use of long-acting reversible contraception (LARC) among Australians of reproductive age. Methods A sample of 18- to 50-year-old women and men (N = 2235) was randomly recruited from the Australian electoral roll in 2013. Respondents completed a self-administered, anonymous questionnaire. Data were weighted to reduce non-response bias. Factors associated with perceived reliability and consideration of use of LARC were identified in multivariable analyses. Results Most respondents had heard of implants (76.5%) and intrauterine contraception (63.7%). However, most did not think implants (56.3%) or IUDs (63.9%) were reliable and would not consider using implants (71.6%) or IUDs (77.5%). Those significantly more likely to perceive LARC as reliable were younger, did not regard religion as important in fertility choices, had private health insurance, had been pregnant and had had an abortion; and women who had a partner. Those more likely to consider using LARC were younger and did not regard religion as important in fertility choices; women who had private health insurance, lived in an area of socioeconomic advantage and had had an abortion; and men without a partner, born in Australia and comfortable talking to a health care provider about contraceptive matters. Conclusions Despite high awareness of LARC among Australian adults, its perceived reliability and willingness to use it remain low in certain groups. Targeted interventions that aim to increase knowledge of the benefits and reliability of LARC and allow informed use are recommended. PMID:26043118

  20. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy.

    PubMed

    Owen, Andrew; Rannard, Steve

    2016-08-01

    Advances in solid drug nanoparticle technologies have resulted in a number of long-acting (LA) formulations with the potential for once monthly or longer administration. Such formulations offer great utility for chronic diseases, particularly when a lack of medication compliance may be detrimental to treatment response. Two such formulations are in clinical development for HIV but the concept of LA delivery has its origins in indications such as schizophrenia and contraception. Many terms have been utilised to describe the LA approach and standardisation would be beneficial. Ultimately, definitions will depend upon specific indications and routes of delivery, but for HIV we propose benchmarks that reflect perceived clinical benefits and available data on patient attitudes. Specifically, we propose dosing intervals of ≥1week, ≥1month or ≥6months, for oral, injectable or implantable strategies, respectively. This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications. Key technological challenges such as the need for consistency and ease of administration for drug combinations, are also discussed. Finally, the review explores the gaps in knowledge regarding the pharmacology of drug release from particulate-based LA injectable suspensions. A number of hypotheses are discussed based upon available data relating to local drug metabolism, active transport systems, the lymphatics, macrophages and patient-specific factors. Greater knowledge of the mechanisms that underpin drug release and protracted exposure will help facilitate further development of this strategy to achieve the promising clinical benefits. PMID:26916628

  1. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

    PubMed Central

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

    2015-01-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

  2. Long-acting diltiazem HCl for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris.

    PubMed

    Claas, Steven A; Glasser, Stephen P

    2005-05-01

    Hypertension is associated with increased cardio- and cerebrovascular morbidity and mortality; antihypertensive drugs have been shown to reduce the risk of adverse cardio- and cerebrovascular events. These events tend to be more common during the morning hours, a time when both normo- and hypertensives show a circadian peak in blood pressure (BP). Although clinicians have a number of safe and well-tolerated antihypertensive agents in various classes and formulations at their disposal, few are designed to specifically attenuate the morning BP surge while maintaining 24-h efficacy. A novel, once-daily, long-acting formulation of diltiazem HCl (DTZ-LA) has been developed with chronodynamics in harmony with diurnal BP variation. DTZ-LA effectively reduces BP in a dose-dependent fashion over a 24-h dosing interval in patients with moderate-to-severe essential hypertension. When compared with a morning dose, the evening dose is associated with significant and clinically meaningful greater reductions in BP during the morning hours, when adverse cardiovascular events tend to cluster. Evening-dosed DTZ-LA was more effective than morning-dosed amlodipine in reducing morning diastolic BP in African-Americans. Evening-dosed DTZ-LA was also more effective than evening-dosed ramipril in reducing morning BP. Evening dosing of DTZ-LA significantly increased exercise tolerance in patients with angina pectoris over the 24-h interval. DTZ-LA is associated with adverse effects consistent with other diltiazem formulations, and overall is safe and well tolerated, even when titrated to doses of 540 mg/day. PMID:15934903

  3. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    PubMed Central

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  4. Stabilization of enzymes through encapsulation in liposomes.

    PubMed

    Yoshimoto, Makoto

    2011-01-01

    Phospholipid vesicle (liposome) offers an aqueous compartment surrounded by lipid bilayer membranes. Various enzyme molecules were reported to be encapsulated in liposomes. The liposomal enzyme shows peculiar catalytic activity and selectivity to the substrate in the bulk liquid, which are predominantly derived from the substrate permeation resistance through the membrane. We reported that the quaternary structure of bovine liver catalase and alcohol dehydrogenase was stabilized in liposomes through their interaction with lipid membranes. The method and condition for preparing the enzyme-containing liposomes with well-defined size, lipid composition, and enzyme content are of particular importance, because these properties dominate the catalytic performance and stability of the liposomal enzymes. PMID:20865384

  5. Liposomal nanocarriers for plasminogen activators.

    PubMed

    Koudelka, Stepan; Mikulik, Robert; Mašek, Josef; Raška, Milan; Turánek Knotigová, Pavlína; Miller, Andrew D; Turánek, Jaroslav

    2016-04-10

    Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward. PMID:26876783

  6. Phospholipid liposomes functionalized by protein

    NASA Astrophysics Data System (ADS)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

    2015-03-01

    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

  7. Implications of Intrathecal Chemotherapy for Anaesthesiologists: A Brief Review

    PubMed Central

    Nair, Abhijit

    2016-01-01

    Intrathecal chemotherapy is routinely prescribed in medical oncology practice, either for prophylaxis or for treatment of leptomeningeal disease due to a primary haematological disease or a metastatic disease due to any other malignancy. As these groups of patients are coagulopathic either because of the disease per se or due to systemic chemotherapy, lumbar puncture in them is considered challenging and is expected to be performed by an anaesthesiologist because of their expertise in this procedure. However, the challenge is not only in performing the lumbar puncture safely but also in dealing with other issues like explaining and handling complications that can happen either due to the drug injected intrathecally or due to a neurodeficit occurring either due to the underlying coagulopathy or due to the progression of leptomeningeal disease. PMID:27123363

  8. Use of Intrathecal Fluorescein in Recurrent Meningitis after Cochlear Implantation

    PubMed Central

    Tandon, Swati; Singh, Satinder; Sharma, Shalabh; Lahiri, Asish K.

    2016-01-01

    Introduction: Congenital anomalies of the cochlea and labyrinth can be associated with meningitis and varying degrees of hearing loss or deafness. Despite antibiotics, meningitis remains a life threatening complication. Case Report: We report a case of recurrent meningitis following episodes of otitis media in a cochlear implantee child with bilateral vestibulocochlear malformation, due to fistula in the stapes footplate. Intrathecal fluorescin was used to identify the leak site. Conclusion: Recurrent meningitis can indicate for possible immunological or anatomical abnormalities as well for chronic parameningeal infections. Intraoperative use of intrathecal fluorescin is an ideal investigative tool to demonstrate cerebrospinal fluid (CSF) leak site in patients in whom other investigations fail to do so. PMID:27429952

  9. Catheter Obstruction of Intrathecal Drug Administration System -A Case Report-

    PubMed Central

    Rhee, Seok Myeon; Choi, Eun Joo; Lee, Pyung Bok

    2012-01-01

    Intrathecal drug administration system (ITDAS) can reduce the side effects while increasing the effectiveness of opioids compared to systemic opioid administration. Therefore, the use of ITDAS has increased in the management of cancer pain and chronic intractable pain. Catheter obstruction is a serious complication of ITDAS. Here, we present a case of catheter obstruction by a mass formed at the side hole and in the lumen. A 37-year-old man suffering from failed back surgery syndrome received an ITDAS implantation, and the ITDAS was refilled with morphine every 3 months. When the patient visited the hospital 18 months after ITDAS implantation for a refill, the amount of delivered morphine sulfate was much less than expected. Movement of the pump rotor was examined with fluoroscopy; however, it was normal. CSF aspiration through the catheter access port was impossible. When the intrathecal catheter was removed, we observed that the side hole and lumen of the catheter was plugged. PMID:22259717

  10. Unusual placement of intrathecal baclofen pumps: report of two cases.

    PubMed

    Devine, Oliver; Harborne, Andrew; Lo, William B; Weinberg, Daniel; Ciras, Mahesh; Price, Rupert

    2016-01-01

    Intrathecal baclofen delivery via implantable pump represents an important modality for symptomatic relief in patients with chronic spasticity. Pumps are routinely implanted subcutaneously in the anterior abdominal wall. We describe two unusual cases where skin-related complications necessitated revision surgery in order to relocate the pump to alternative sites. The first patient was an international power canoeist, whose strenuous exercise programme interfered with his pump's original siting. The second patient was a cachectic university student with a history of cerebral palsy, who maintained low body mass despite attempted weight gain. The relocation of these two intrathecal devices to the medial compartment of the right thigh and right iliac fossa, respectively, is described. PMID:26592253

  11. Stability of dry liposomes in sugar glasses.

    PubMed Central

    Sun, W Q; Leopold, A C; Crowe, L M; Crowe, J H

    1996-01-01

    Sugars, particularly trehalose and sucrose, are used to stabilize liposomes during hydration (freeze-drying and air-drying). As a result, dry liposomes are trapped in a sugar glass, a supersaturated and thermodynamically unstable solid solution. We investigated the effects of the glassy state on liposome fusion and solute retention in the dry state. Solute leakage from dry liposomes was extremely slow at temperatures below the glass transition temperature (Tg); however, it increased exponentially as temperature increased to near or above the Tg, indicating that the glassy state had to be maintained for dry liposomes to retain trapped solutes. The leakage of solutes from dry liposomes followed the law of first-order kinetics and was correlated linearly with liposome fusion. The kinetics of solute leakage showed an excellent fit with the Arrhenius equation at temperatures both above and below the Tg, with a transitional break near the Tg. The activation energy of solute leakage was 1320 kJ/mol at temperatures above the Tg, but increased to 1991 kJ/mol at temperatures below the Tg. The stabilization effect of sugar glass on dry liposomes may be associated with the elevated energy barrier for liposome fusion and the physical separation of dry liposomes in the glassy state. The half-life of solute retention in dry liposomes may be prolonged by storing dry liposomes at temperatures below the Tg and by increasing the Tg of the dry liposome preparation. PMID:8785336

  12. Dorsal column myelopathy following intrathecal chemotherapy for acute lymphoblastic leukemia

    PubMed Central

    Joseph, Prathap Jacob; Reyes, Maria Regina

    2014-01-01

    Objective/context To describe a distinctive clinical and radiographic pattern of myelopathy following intrathecal chemotherapy. Myelopathy is a rare complication of intrathecal chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL). We present a 42-year-old female with T-cell ALL who developed a myelopathy primarily involving the dorsal columns. Method Case report and literature review. Findings Within 24 hours of an injection of intrathecal methotrexate, cytarabine, and hydrocortisone, the patient developed ascending lower limb numbness and balance difficulties progressing to the inability to ambulate. Clinical examination showed profound loss of lower limb proprioception and light touch sensation below T5, mild proximal limb weakness, but preserved pinprick and temperature sensation with intact bowel and bladder function. Initial thoracic and lumbar spine magnetic resonance imaging (MRI) at 1 week revealed no abnormalities. However, repeat imaging at 6 weeks showed abnormal signal in the posterior cord with sparing of the anterior and lateral columns, diffusely involving the lower cervical cord through the conus medullaris. Dermatomal somatosensory-evoked potential (DSEP) conduction abnormalities were consistent with thoracic myelopathy. An empiric trial of high-dose intravenous corticosteroids during inpatient rehabilitation more than 6 weeks later produced no significant clinical improvement. Conclusion/clinical relevance Preferential and persistent dorsal column myelopathy is a distinctive clinical and radiographic presentation of a rare complication of intrathecal chemotherapy. The MRI abnormalities were initially absent, but evolved to consist of multi-level spinal cord T2 and STIR hyperintensity with regional gadolinium enhancement. DSEPs more accurately reflected the clinical level of spinal cord dysfunction. PMID:24090227

  13. [Treatment of severe tetanus by repeated intrathecal injections of baclofen].

    PubMed

    Vitris, M; Saissy, J M; Demaziere, J; Seck, M; Ndiaye, M; Gaye, N; Marcoux, L

    1991-01-01

    A case of tétanos was treated through intrathecal injections of baclofen. This new technique was pioneered in Anglo-saxon countries and has made it possible in the present case to success fully treat a Mollaret's third-stage generalized tetanus, without a tracheotomy or controlled ventilation. Because of its simplicity low cost, this technique could be another way of treating African tetanus. PMID:1842757

  14. Comparative Pharmacokinetics of Continuous and Conventional Intrathecal Amphotericin B in Rabbits

    PubMed Central

    Fang, Min; Ma, An De; Wang, Li; Li, Guo Liang; Qiu, Ai Zhu; Pan, Zhi Yong; Wang, Yuan Yuan; Liu, Xiao Jia

    2012-01-01

    We previously reported a new effective therapy, continuous intrathecal amphotericin B (AMB), for the treatment of cryptococcal meningitis, which had fewer side effects and complications than conventional intrathecal AMB. In this study, the pharmacokinetics of continuous intrathecal administration and conventional intrathecal AMB were compared in rabbits, providing a pharmacokinetic basis for the use of continuous intrathecal AMB therapy. The AMB concentration in the cerebrospinal fluid (CSF), sampled via an inserted cisterna magna catheter, was determined by a liquid chromatography-tandem mass spectrometry assay. The results revealed significant pharmacokinetic differences between the two groups. In the continuous intrathecal group (0.15 mg/kg/24 h), the concentration of AMB peaked 7.01 μg/ml at 4 h and then decreased to a stable level of 1.0 to 1.34 μg/ml, with no neurological impairments, while in the conventional intrathecal group (0.015 mg/kg), the drug concentration reached a peak of 3.41 μg/ml at 1 h and then decreased progressively, with fever and neurological impairments, including convulsion and paralysis. The pharmacokinetic results indicated that the continuous intrathecal AMB is a more effective and safe therapy than the conventional intrathecal AMB, with comparatively rational pharmacokinetics and fewer neurological impairments. PMID:22850516

  15. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

    PubMed Central

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, Cmax, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0–∞) of both products. In the case of the time to maximum concentration (Tmax), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC0–∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the Tmax (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ and Tmax values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  16. Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness

    PubMed Central

    2013-01-01

    Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance

  17. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan.

    PubMed

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-08-11

    In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan-both working with Options Consultancy Services-have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from offering services

  18. Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses

    PubMed Central

    2013-01-01

    Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most

  19. A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide

    PubMed Central

    Gurung, Tara; Shyangdan, Deepson S; O’Hare, Joseph Paul; Waugh, Norman

    2015-01-01

    Background Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. Methods MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. Results Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: −1.5%/−1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg −1.22%/−1.01%; sitagliptin: −0.6%). HbA1c change was greater with dulaglutide 1.5 mg (−1.08%) than with glargine (−0.63%), but not with dulaglutide 0.75 mg (−0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. Conclusion

  20. A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia.

    PubMed

    Li, Huafang; Rui, Qing; Ning, Xiaoping; Xu, Haiyan; Gu, Niufan

    2011-06-01

    This open-label, rater-blinded, parallel-group study was designed to evaluate noninferiority of paliperidone palmitate (PP), a once-monthly injectable atypical antipsychotic, to once-biweekly risperidone long-acting injectable (RIS-LAI) in adult Chinese patients with acute schizophrenia. Eligible Chinese adults (N=452) with schizophrenia were randomized (1:1) to either PP (N=229; deltoid injections on day 1 [150 mg eq.] and day 8 [100 mg eq.]; then once-monthly deltoid or gluteal injections, flexibly dosed [50, 100, or 150 mg eq.]), or RIS-LAI (N=223; once-biweekly gluteal injections, flexibly dosed [25, 37.5 or 50 mg]). RIS-LAI-treated patients received oral risperidone supplementation (1-6 mg/day) at initiation and with RIS-LAI dose increases. Mean (SD) Positive and Negative Syndrome Scale (PANSS) total score at baseline was 83.2 (12.44). Mean (SD) change from baseline to endpoint in PANSS total scores (primary efficacy measure) was: -23.6 (16.28) for PP group and -26.9 (15.43) for RIS-LAI group. PP was noninferior to RIS-LAI (least squares mean difference [95% CI]: -2.3 [-5.20; 0.63]; predetermined non-inferiority margin: -5.5). Mean (SD) change from baseline to endpoint in Clinical Global Impression-Severity scale score was: -1.5 (1.24; PP group), -1.7 (1.16; RIS-LAI group) and in Personal and Social Performance Scale scores was: 16.8 (14.76; PP group), 18.6 (13.92; RIS-LAI group). The incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups (73% [PP]; 75% [RIS-LAI]). The most common TEAEs were akathisia, tremor, and insomnia. The study demonstrated the noninferiority of PP (50-150 mg eq., flexibly dosed, without oral paliperidone supplementation) to risperidone-LAI (25-50 mg, flexibly dosed, with oral risperidone supplementation) for the treatment of acute schizophrenia in adult Chinese patients. PP injections were generally tolerable, and no new safety signals were detected in this population. PMID:21315787

  1. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan

    PubMed Central

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-01-01

    ABSTRACT In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan—both working with Options Consultancy Services—have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from

  2. Bilateral subdural hygromas following administration of intrathecal methotrexate chemotherapy.

    PubMed

    Lewis, Heledd; Mahdi, Ali Jassem; Rowntree, Clare

    2015-01-01

    We report the case of a previously well 58-year-old man who presented with headache and confusion 4 days postadministration of intrathecal methotrexate. He was undergoing intensive chemotherapy (CODOX-M/IVAC, cyclophosphamide, doxorubicin, vincristine, methotrexate, etoposide, ifosfamide, cytarabine) for the treatment of leukaemic phase CD20 negative diffuse large B-cell lymphoma. A CT of the head demonstrated the presence of bilateral subdural hygromas complicated by haemorrhage resulting from coexisting chemotherapy induced thrombocytopenia. Surgical drainage of the hygroma was undertaken but the patient died of overwhelming sepsis. In patients with high-risk lymphoma, directed central nervous system (CNS) therapy is administered either systemically or intrathecally. It is thought that subdural hygromas result from cerebrospinal fluid (CSF) accumulation in the inner dural layers of the cerebral convexities from CSF leak and reduction in CSF pressure post-lumbar puncture. We describe a rare but potentially fatal complication of intrathecal chemotherapy that haemato-oncologists need to be mindful of. PMID:26002663

  3. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    PubMed

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  4. Intrathecal ziconotide: a review of its use in patients with chronic pain refractory to other systemic or intrathecal analgesics.

    PubMed

    Sanford, Mark

    2013-11-01

    Ziconotide (Prialt(®)) is a synthetic conopeptide analgesic that acts by selectively antagonizing N-type voltage-gated calcium channels. Intrathecal ziconotide is the only non-opioid intrathecal analgesic that is FDA-approved for use in patients with treatment-refractory, chronic pain. The efficacy of intrathecal ziconotide was demonstrated in randomized, double-blind, placebo-controlled trials in patients with treatment-refractory noncancer-related pain or cancer- or AIDS-related pain. Across trials, ziconotide recipients had significantly greater reductions in pain intensity during ziconotide treatment than those receiving placebo (primary endpoint). At the end of the titration period, approximately one-sixth to one-third of patients with noncancer chronic pain and one-half with cancer- or AIDS-related pain who received ziconotide reached a pain response threshold (≥30 % reduction in the pain intensity score). In ziconotide responders, analgesic effects were enduring, with some patients continuing treatment over extended periods. Across trials, the chief tolerability concerns in ziconotide recipients during the titration phase and during extended treatment were related to CNS adverse events. These were mostly of mild to moderate intensity, although serious adverse events were commonly attributed to ziconotide treatment, especially in trials with rapid ziconotide titration and that permitted higher dosages. In general, clinically important non-CNS adverse events were infrequent, and during the ziconotide titration phase, relatively few patients discontinued treatment because of adverse events. Ongoing research will assess various strategies for selecting patients for ziconotide treatment and for enhancing its efficacy and tolerability. At the present time, intrathecal ziconotide provides a treatment option for patients with severe, unremitting pain who have failed to respond to other intensive analgesic regimens. PMID:23999971

  5. Environment-Responsive Multifunctional Liposomes

    PubMed Central

    Kale, Amit A.; Torchilin, Vladimir P.

    2012-01-01

    Liposomal nanocarriers modified with cell-penetrating peptide and a pH-sensitive PEG shield demonstrate simultaneously a better systemic circulation and site-specific exposure of the cell-penetrating peptide. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE), while cell-penetrating peptide (TATp) was added as TATp-PEG-PE conjugate. Under normal conditions, liposome-grafted PEG “shielded” liposome-attached TATp moieties, since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes accumulate in targets via the EPR effect, but inside the “acidified” tumor or ischemic tissues lose their PEG coating because of the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. pH-responsive behavior of these constructs is successfully tested in cell cultures in vitro as well as in tumors in experimental mice in vivo. These nanocarriers also showed enhanced pGFP transfection efficiency upon intratumoral administration in mice, compared to control pH nonsensitive counterpart. These results can be considered as an important step in the development of tumor-specific stimuli-sensitive drug and gene delivery systems. PMID:20072884

  6. Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding

    PubMed Central

    Chen, Haojun; Wang, Guohao; Lang, Lixin; Jacobson, Orit; Kiesewetter, Dale O.; Liu, Yi; Ma, Ying; Zhang, Xianzhong; Wu, Hua; Zhu, Lei; Niu, Gang; Chen, Xiaoyuan

    2016-01-01

    The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs. PMID:26877782

  7. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.

    PubMed

    Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

    2005-01-01

    Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and

  8. [Side effects of treatment with the long-acting gonadorelin agonist triptorelin in a case of paraphilia].

    PubMed

    Hoogeveen, J H; van der Veer, E

    2007-01-01

    A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regimen needs to be revised. PMID:17290340

  9. Knowledge and Perception on Long Acting and Permanent Contraceptive Methods in Adigrat Town, Tigray, Northern Ethiopia: A Qualitative Study

    PubMed Central

    Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice. PMID:25140252

  10. Liposome-like Nanostructures for Drug Delivery

    PubMed Central

    Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

    2013-01-01

    Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

  11. Design of liposomal formulations for cell targeting.

    PubMed

    Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

    2015-12-01

    Liposomes have gained extensive attention as carriers for a wide range of drugs due to being both nontoxic and biodegradable as they are composed of substances naturally occurring in biological membranes. Active targeting for cells has explored specific modification of the liposome surface by functionalizing it with specific targeting ligands in order to increase accumulation and intracellular uptake into target cells. None of the Food and Drug Administration-licensed liposomes or lipid nanoparticles are coated with ligands or target moieties to delivery for homing drugs to target tissues, cells or subcellular organelles. Targeted therapies (with or without controlled drug release) are an emerging and relevant research area. Despite of the numerous liposomes reviews published in the last decades, this area is in constant development. Updates urgently needed to integrate new advances in targeted liposomes research. This review highlights the evolution of liposomes from passive to active targeting and challenges in the development of targeted liposomes for specific therapies. PMID:26454541

  12. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children

    PubMed Central

    Ni Chroinin, Muireann; Lasserson, Toby J; Greenstone, Ilana; Ducharme, Francine M

    2014-01-01

    Background Long-acting ß2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children. Objectives To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma. Search methods We searched the Cochrane Airways Group Asthma Trials Register (May 2008). Selection criteria We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals. Data collection and analysis Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. Main results A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS: (1)The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV1 at baseline was 80% of predicted or above in 10 studies; FEV1 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1

  13. Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. Method: The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan–Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Conclusions: Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time. PMID:26913175

  14. Intrathecal baclofen for the treatment of spasticity of cerebral origin.

    PubMed

    Disabato, Jennifer; Ritchie, Anne

    2003-01-01

    Nurses monitoring children receiving intrathecal baclofen therapy can assist with management of these patients by being aware of possible complications related to a change in tone, medication withdrawal, or overdose. The tone management team relies on family care providers, school nurses, ambulatory clinic nurses, and outside physical and occupational therapists to provide information and updates on changes in patient status as needed. Close collaboration and communication regarding the child and his/her response to ITB is essential to providing safe and effective care for this challenging population of patients. PMID:12715404

  15. [Intrathecal baclofen therapy and management of severe spasticity].

    PubMed

    Naito, Yutaka

    2014-09-01

    Continuous infusion of intrathecal baclofen (ITB), via implanted pump, is a powerful tool in the management of severe spasticity in neurological disorders. The advantages of ITB therapy are that it is non-destructive, reversible, and programmable, allowing for neuromodulation. Patients reported significant subjective improvements and decreases in muscle tone after baclofen injection, but excessive doses of ITB resulted in motor weakness. Few complications and adverse effects were reported. ITB therapy appears to be a promising treatment to improve residual motor control in patients with severe spasticity. PMID:25200576

  16. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier

    PubMed Central

    Wang, Xiang; Liu, Ping; Yang, Weixiao; Li, Lu; Li, Peijing; Liu, Zheng; Zhuo, Zhongxiong; Gao, Yunhua

    2014-01-01

    Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 μm in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 μg/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 μg/g) > MTX alone (6.97±0.75 μg/g) > MTX-liposome-coupled microbubbles (2.92±0.39 μg/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (P<0.01). These results suggest that MTX-liposome-coupled microbubbles may hold great promise as new and effective therapies for primary central nervous system lymphoma and other central

  17. Capacious and programmable multi-liposomal carriers

    NASA Astrophysics Data System (ADS)

    Yaroslavov, Alexander A.; Sybachin, Andrey V.; Zaborova, Olga V.; Migulin, Vasiliy A.; Samoshin, Vyacheslav V.; Ballauff, Matthias; Kesselman, Ellina; Schmidt, Judith; Talmon, Yeshayahu; Menger, Fredric M.

    2015-01-01

    Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes.Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational

  18. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  19. Pipotiazine palmitate: an evaluation of a new long acting intramuscular antipsychotic agent in severely ill schizophrenic patients.

    PubMed

    Gallant, D M; Mielke, D; Bishop, G; Oelsner, T; Guerrero-Figueroa, R

    1975-04-01

    Findings in this study support earlier investigations in attesting to the antipsychotic efficacy and relatively low toxicity of pipotiazine palmitate. Results with all efficacy measures utilized were consistent in indicating a high level of efficacy for this investigational compound. Pipotiazine palmitate apparently has an average duration of action that extends beyond 4 weeks in severely ill schizophrenic patients. This particular long acting IM antipsychotic preparation appears to have an even longer duration of activity than some of the other available standard long acting agents. The optimal dosage range for severely ill schizophrenic patients appears to be between 100 and 600 mg once monthly. While this type of drug (as is the case with many antipsychotic drugs) does reduce the psychotic symptomatology and improves the thought associations sufficient to enable the patient to leave the hospital, it should be re-emphasized that socioeconomic and guidance counseling services are necessary to maintain the patient in the community. The availability of this type of long acting preparation is not only economical in terms of nursing care and hospital cost but it should also increase the efficacy of psychopharmacologic treatment of schizophrenics by reducing both patient errors and staff errors in administration of medication. In addition, this IM preparation should prove to be of invaluable help in maintaining the schizophrenic patient in his community by reducing the relapse and the rehospitalization rates. It should be noted that there are schizophrenic patients who either absorb compounds from the gastrointestinal tract in a very poor manner or too rapidly metabolize the antipsychotic agents with resultant suboptimal blood levels and these subjects may be called "drug refractory." This type of long acting medication is an ideal preparation for the schizophrenic patient who has these types of absorption or metabolic problems since the "circulatory pass" through the

  20. Potential long-acting anticonvulsants. 1; Synthesis and activity of succinimides containing an alkylating group at the 2 position.

    PubMed

    Kornet, M J; Crider, A M; Magarian, E O

    1977-03-01

    The synthesis of succinimide derivatives in which alkylating groups have been attached to the 2 positions of the ring or to the para position of the 2-phenyl substituent is described. The alkylating groups used were (a) alpha-haloacetyl, (b) alpha-haloacetamido, (c) maleimido, and (d) maleamyl. These compounds were prepared as potential long-acting anticonvulsants. Several of these derivatives exhibited activity against metrazole-induced seizures comparable to phensuximde, The maleimide 16 and the bromoacetamido derivative 23 exhibited a duration of action of at least 3.5 h. PMID:845873

  1. Effects of intrathecal anandamide on somatosensory evoked responses in rats.

    PubMed

    Bir, Levent Sinan; Ercan, Sevim

    2006-02-01

    Anandamide, endogenous ligand of cannabinoid receptors produces similar effects of cannabinoids via CB1 receptors in the central nervous system. Its effect on ascending pathways of somatosensory conduction and somatosensory cortex is not known. The aim of this study was to determine the effects of anandamide on somatosensory evoked potentials (SEP). In this study, 24 Wistar male rats were used. The rats were divided into 4 groups. At the beginning, sciatic nerve stimulated scalp SEP traces were obtained from all of the rats. Later, 0.02 cm(3) anhydrous ethanol, 100 microg/kg, 200 microg/kg and 400 microg/kg anandamide dissolved in anhydrous ethanol were injected intrathecally to the first (control), second, third and fourth groups, respectively. Five minutes later, second SEP traces were started. In every SEP trace, two negative waves (N1, N2) following positive deflections were obtained. The latency and amplitudes of these waves assessed were compared in each group. In control and second groups, the parameters of these waves before and after the injections were not significantly different. However, in the third and fourth groups, latencies of N1 and N2 after injections were found significantly longer. This effect was dose dependent. In any of the groups, no significant changes were detected in the amplitudes after injections. In conclusion, anandamide, when injected intrathecally in pharmacological doses caused an induction of moderate conduction delay in SEP systems. PMID:16289169

  2. [Anesthetic Management of an Adrenoleukodystrophy Patient for Intrathecal Baclofen Therapy].

    PubMed

    Hashimoto, Yuichi; Takahashi, Kei; Yamamoto, Yuko; Ogata, Tokiko; Arai, Takero; Okuda, Yasuhisa

    2016-04-01

    A 34-year-old man with adrenoleukodystrophy (ALD) was scheduled for pump system insertion of intrathecal baclofen therapy under general anesthesia. ALD, a rare genetic disorder, is associated with a total body increase in long chain fatty acids caused by defective degradation, and includes various nervous system abnormalities, muscular weakness, in addition to adrenal insufficiency. He had contracture of the both legs, and muscular weakness of the left hand, and Mallampati class III, but no respiratory disability. In the operating room, we administered hydrocortisone 100 mg for steroid coverage, and low-dose midazolam, and fentanyl. As spontaneous breathing remained, we could easily see epiglottis and arytenoid cartilage by McGRATH. Therefore we selected rapid-induction of anesthesia with thiamylal, and rocuronium 40 mg, under cricoid pressure. We avoided propofol. Anesthsia was maintained with sevoflurane and remifentanil, monitoring BIS and train of four. No more rocuronium was administered, and anesthesia was uneventful. Intrathecal baclofen therapy is given to patients who have severe contracture. When we selected general anesthesia, we should be aware of the possibility of muscular weakness, and cannot intubate cannot ventilate scenario. PMID:27188115

  3. Intrathecal rimantadine induces motor, proprioceptive, and nociceptive blockades in rats.

    PubMed

    Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

    2016-04-01

    The purpose of the experiment was to evaluate the local anesthetic effect of rimantadine in spinal anesthesia. Rimantadine in a dose-dependent fashion was constructed after intrathecally injecting the rats with four different doses. The potency and duration of rimantadine were compared with that of the local anesthetic lidocaine at producing spinal motor, nociceptive, and proprioceptive blockades. We demonstrated that intrathecal rimantadine dose-dependently produced spinal motor, nociceptive, and proprioceptive blockades. On the 50% effective dose (ED50) basis, the ranks of potencies at inducing spinal motor, nociceptive, and proprioceptive blockades was lidocaine>rimantadine (P<0.01). Rimantadine exhibited more nociceptive block (ED50) than motor block (P<0.05). At equi-anesthetic doses (ED25, ED50, and ED75), the spinal block duration produced by rimantadine was longer than that produced by lidocaine (P<0.01). Furthermore, rimantadine (26.52μmol/kg) prolonged the nociceptive nerve block more than the motor block (P<0.001). Our preclinical data showed that rimantadine, with a more sensory-selective action over motor block, was less potent than lidocaine. Rimantadine produced longer duration in spinal anesthesia when compared with lidocaine. PMID:26949181

  4. Intrathecal Analgesia for Chronic Refractory Pain: Current and Future Prospects.

    PubMed

    Smyth, Catherine; Ahmadzai, Nadera; Wentzell, Jason; Pardoe, Ashley; Tse, Andrew; Nguyen, Tiffany; Goddard, Yvette; Nair, Shona; Poulin, Patricia A; Skidmore, Becky; Ansari, Mohammed T

    2015-11-01

    The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients. There are far more systematic reviews than high-quality primary comparative studies of the IDDS vs. conventional pain treatment. Existing clinical practice recommendations are best viewed as expert opinion with competing interests. This article will review the existing literature for indications, contraindications, consensus statements, different technologies, and complications of the IDDS. Although approved analgesics for IDDS delivery are limited to morphine and ziconotide, many other analgesics, alone or in combination, are routinely used in this setting. This review will also focus on the pharmacology, clinical efficacy, and safety of intrathecal medications extensively used in clinical practice; including agents approved, unapproved, and under development. PMID:26501979

  5. Application of Liposomes in Some Dairy Products.

    PubMed

    Khanniri, E; Bagheripoor-Fallah, N; Sohrabvandi, S; Mortazavian, A M; Khosravi-Darani, K; Mohammad, R

    2016-01-01

    The application of liposomes as potential carriers to deliver food components is considerably an innovative technology. While the application of liposome technology has been very limited to date, researches indicating the potential of liposomes for improving the flavor of ripened cheese using accelerated methods, the targeted delivery of functional food ingredients, the synergistic delivery of ascorbic acid and tocopherols for promoting antioxidant activity in foods, and the stabilization of minerals (such as iron) in milk have been performed. In the food industry, liposomes and nanoliposomes have been employed to encapsulate flavoring and nutritive agents, and also, they have been suitable candidates to deliver antimicrobials. In this paper, application of lipase, proteinase, nisin, and flavor-containing liposomes in products during the processing (such as cheese maturity) as well as the application of liposomes-encapsulated micronutrients (such as iron) in milk are reviewed. PMID:25574577

  6. Pharmacokinetics of a long-acting oxytetracycline preparation in ring-necked pheasants, great horned owls, and Amazon parrots.

    PubMed

    Teare, J A; Schwark, W S; Shin, S J; Graham, D L

    1985-12-01

    After a single IV or IM dose of a long-acting oxytetracycline (OTC) preparation, serum concentrations were determined at various times in the ring-necked pheasant, great horned owl, and Amazon parrot. Pharmacokinetic parameters, including serum half-life (t1/2) and apparent volume of distribution (Vd) were calculated from the OTC concentration-time curves for each species and route of administration. Significant differences (P less than 0.05) were found in the t1/2 and Vd parameters between species and routes of administration. Dosage regimens to maintain minimum OTC concentration of 5 micrograms/ml of serum were calculated from the t 1/2 and Vd values obtained, using steady-state pharmacokinetics. In the pheasant, the calculated mean IV dose was 23 mg/kg of body weight every 6 hours, whereas the mean IM dose was 43 mg/kg every 24 hours. The mean IM dose was 16 mg/kg every 24 hours for the owl and 58 mg/kg every 24 hours for the parrot. The small volumes required for treatment, the long-dosing interval obtainable, and the broad spectrum of antimicrobial activity of the long-acting OTC preparation studied offered major advantages over other antibiotics commonly used in treating avian species. PMID:4083606

  7. Long-Acting Reversible Contraceptive Use in Urban Women From a Title X–Supported Boston Community Health Center

    PubMed Central

    Ricciotti, Hope A.; Dodge, Laura E.; Ramirez, Christina I.; Barnes, Katherine; Hacker, Michele R.

    2015-01-01

    Background Unintended and adolescent pregnancy disproportionately affects minority populations, but the effect of age, race and ethnicity on the use of long-acting reversible contraception (LARC) has not been well studied. Objective The objective of this pilot study was to examine LARC use over a 5-year period among women receiving care at a Boston community health center. Methods Retrospective cohort study of LARC method use among black, Hispanic, and white women receiving care at the Dimock Center from 2006 to 2010. Results This study included 276 women (60.1% black, 18.5% Hispanic, and 9.1% white). LARC was not used as a first-line method in the majority (96.0%), regardless of age, race, and ethnicity; yet nearly half identified a long-acting contraceptive as their method of choice. Conclusions The findings of this pilot study reveal opportunities to reduce unintended pregnancy through increased LARC use, which may be accomplished by provider and patient education. PMID:25301380

  8. Long-acting injectables and risk for rehospitalization among patients with schizophrenia in the home care program in Taiwan.

    PubMed

    Ju, Po-Chung; Chou, Frank Huang-Chih; Lai, Te-Jen; Chuang, Po-Ya; Lin, Yung-Jung; Yang, Ching-Wen Wendy; Tang, Chao-Hsiun

    2014-02-01

    We aimed at evaluating the relationship between medication and treatment effectiveness in a home care setting among patients with schizophrenia. Patients with schizophrenia hospitalized between 2004 and 2009 with a primary International Classification of Diseases, Ninth Revision, Clinical Modification code of 295 were identified from Psychiatric Inpatient Medical Claims Data released by the National Health Research Institute in Taiwan. Patients who joined the home care program after discharge and were prescribed long-acting injection (LAI) (the LAI group) or oral antipsychotic medications (the oral group) were included as study subjects. The final sample for the study included 810 participants in the LAI group and 945 in the oral group. Logistic regression was performed to examine the independent effect of LAI medication on the risk for rehospitalization within the 12-month observation window after controlling for patient and hospital characteristics and propensity score quintile adjustment. The unadjusted odds ratio for rehospitalization risk was 0.80 (confidence interval, 0.65-0.98) for the LAI group compared to the oral group. The adjusted odds ratio was further reduced to 0.78 (confidence interval, 0.63-0.97). Results remained unchanged when the propensity score quintiles were entered into the regression for further adjustment. In a home care setting, patients treated with long-acting antipsychotic agents are at a significantly lower risk for psychiatric rehospitalization than those treated with oral medication. Consequently, LAI home-based treatment for the prevention of schizophrenia relapse may lead to substantial clinical and economic benefits. PMID:24145217

  9. Rapid nongenomic actions of inhaled corticosteroids on long-acting β(2)-agonist transport in the airway.

    PubMed

    Horvath, Gabor; Mendes, Eliana S; Schmid, Nathalie; Schmid, Andreas; Conner, Gregory E; Fregien, Nevis L; Salathe, Matthias; Wanner, Adam

    2011-12-01

    Corticosteroids inhibit organic cation transporters (OCTs) that play an important role in drug absorption, tissue distribution and elimination. Corticosteroid sensitivity of bronchodilator trafficking in the airway tissue, however, is poorly understood. To assess the effects of inhaled corticosteroids on airway absorption and disposal mechanisms of long-acting β(2)-agonists, human airway epithelial and smooth muscle cell uptake of tritiated formoterol and salmeterol was measured in vitro. Corticosteroids caused a rapid, concentration-dependent inhibition of uptake of the cationic formoterol by airway smooth muscle cells, but not airway epithelial cells. Uptake of the non-charged lipophilic salmeterol was corticosteroid-insensitive in both cell types. In smooth muscle cells, inhaled corticosteroids inhibited formoterol uptake with a novel potency rank order: des-ciclesonide > budesonide > beclomethasone 17-monopropionate > beclomethasone dipropionate > ciclesonide > fluticasone. The inhibitory action was rapidly reversible, and was not enhanced by prolonged corticosteroid exposure or sensitive to a transcription inhibitor. Suppression of OCT3 expression using lentivirus-mediated production of shRNA reduced corticosteroid sensitivity of formoterol uptake by smooth muscle cells. Our data support a corticosteroid insensitive absorption and a corticosteroid-sensitive disposition mechanism for cationic long-acting β(2)-agonist bronchodilators in the airway. Potency rank order and other 'classical' features of anti-inflammatory effects do not apply to inhaled corticosteroids' rapid drug transport actions. PMID:21914487

  10. Europium chelate-loaded liposomes: a tool for the study of binding and integrity of liposomes.

    PubMed

    Orellana, A; Laukkanen, M L; Keinänen, K

    1996-10-01

    Using the biotin-streptavidin interaction as a model, we investigated the suitability of lanthanide chelates as encapsulated liposomal labels in liposome-based binding assays. Large unilamellar phospholipid:cholesterol liposomes containing europium-DTPA chelate and biotinylated phosphatidylethanolamine were prepared by detergent dialysis. The resulting Eu-liposomes ([symbol: see text] 120 nm) bound specifically to streptavidin in microtiter wells as measured by time-resolved fluorometric assay (TRF). The intensity of fluorescence released from the bound liposomes was dependent on the concentration of biotin in the liposome membrane, the concentration of europium entrapped in the liposomes, the incubation time and the amount of liposomes used in the assay. The sensitivity of the TRF assay allowed the detection of binding of attomole quantities of liposomes. The streptavidin-immobilised liposomes subjected to porcine pancreatic phospholipase A2 (EC 3.1.1.4) and detergents displayed a dose-dependent release of the encapsulated europium. Lanthanide-chelate-liposomes should prove useful for studies addressing binding and stability of liposomes. PMID:8865811

  11. Intrathecal cannabinoid-1 receptor agonist prevents referred hyperalgesia in acute acrolein-induced cystitis in rats

    PubMed Central

    Jones, Marsha Ritter; Wang, Zun-Yi; Bjorling, Dale E

    2015-01-01

    We investigated the capacity of intrathecal arachidonyl-2’-chloroethylamide (ACEA), a cannabinoid-1 receptor (CB1R) agonist, to inhibit referred hyperalgesia and increased bladder contractility resulting from acute acrolein-induced cystitis in rats. 24 female rats were divided into 4 groups: 1) intrathecal vehicle/intravesical saline; 2) intrathecal vehicle/intravesical acrolein; 3) intrathecal ACEA/intravesical saline; and 4) intrathecal ACEA/intravesical acrolein. Bladder catheters were placed 4-6 days prior to the experiment. On the day of the experiment, rats were briefly anesthetized with isoflurane to recover the external end of the cystostomy catheter. After recovery from anesthesia, pre-treatment cystometry was performed, and mechanical sensitivity of the hindpaws was determined. Rats were again briefly anesthetized with isoflurane to inject ACEA or vehicle into the intrathecal space between L5-L6. Beginning 10 minutes after intrathecal injection, saline or acrolein was infused into the bladder for 30 minutes. Post-treatment cystometry and mechanical sensitivity testing were performed. Rats were euthanized, and bladders were collected, weighed, and fixed for histology. The intrathecal vehicle/intravesical acrolein group developed mechanical hyperalgesia with post-treatment mechanical sensitivity of 6 ± 0.3 g compared to pretreatment of 14 ± 0.4 g (p < 0.01). Pre- and post-treatment hind paw mechanical sensitivity was statistically similar in rats that received intrathecal ACEA prior to intravesical infusion of acrolein (15 ± 0.2 g and 14 ± 0.4 g, respectively). Acrolein treatment increased basal bladder pressure and maximal voiding pressure and decreased intercontraction interval and voided volume. However, intrathecal ACEA was ineffective in improving acrolein-related urodynamic changes. In addition, bladder histology demonstrated submucosal and muscularis edema that was similar for all acrolein-treated groups, irrespective of ACEA treatment

  12. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    PubMed Central

    Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

    2015-01-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

  13. Interaction of rotavirus particles with liposomes.

    PubMed

    Nandi, P; Charpilienne, A; Cohen, J

    1992-06-01

    We have studied the interactions of purified viral particles with liposomes as a model to understand the mechanism of entry of rotavirus into the cell. Liposomes, made from pure as well as mixed lipids, that contained encapsulated self-quenching concentrations of the fluorophore carboxyfluorescein (CF) were used. Rotavirus-liposome interactions were studied from the fluorescence dequenching of CF resulting from its release to the bulk solution. Purified infectious double-shelled virus particles induced a concentration- and temperature-dependent release of CF. The rate and extent of CF release was maximum between pH 7.3 and 7.6. The removal of outer structural proteins VP4 and VP7 from virus, which results in the formation of single-shelled particles, prevented virus interaction with liposomes. Rotavirus particles with uncleaved VP4 did not interact with liposomes, but treatment in situ of these particles with trypsin restored the interaction with the liposomes and resulted in CF dequenching. Our data support the view that rotavirus enters the cell through direct penetration of the plasma membrane. In contrast, adenovirus, the only other nonenveloped virus studied by this method, shows the optimum rate of marker release from liposomes at around pH 6 (R. Blumenthal, P. S. Seth, M. C. Willingham, and I. Pastan, Biochemistry 25:2231-2237, 1986). The interaction between rotavirus and liposomes is sensitive to specific divalent metal ions, unlike the adenovirus-liposome interaction, which is independent of them. PMID:1316453

  14. Tumor targeting using liposomal antineoplastic drugs

    PubMed Central

    Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan

    2008-01-01

    During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research. PMID:18488413

  15. Ligand-targeted liposomes for cancer treatment.

    PubMed

    Sapra, Puja; Tyagi, Pradeep; Allen, Theresa M

    2005-10-01

    Selective targeting of ligand-targeted liposomes containing anticancer drugs or therapeutic genes to cell surface receptors expressed on cancer cells is a recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics or gene therapeutics. Some recent advances in the field of ligand-targeted liposomes for the treatment of cancer are summarized including: selection criteria for the receptors to be targeted, choice of targeting ligands and choice of encapsulated therapeutics. Targeting of liposomes to solid tumors, versus angiogenic endothelial cells versus vascular targets is discussed. Ligand-targeted liposomes have shown considerable promise in preclinical xenograft models and are poised for clinical development. PMID:16305440

  16. Liposome adhesion generates traction stress

    NASA Astrophysics Data System (ADS)

    Murrell, Michael P.; Voituriez, Raphaël; Joanny, Jean-François; Nassoy, Pierre; Sykes, Cécile; Gardel, Margaret L.

    2014-02-01

    Mechanical forces generated by cells modulate global shape changes required for essential life processes, such as polarization, division and spreading. Although the contribution of the cytoskeleton to cellular force generation is widely recognized, the role of the membrane is considered to be restricted to passively transmitting forces. Therefore, the mechanisms by which the membrane can directly contribute to cell tension are overlooked and poorly understood. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome spreading generates large traction stresses on compliant substrates. These stresses can be understood as the equilibration of internal, hydrostatic pressures generated by the enhanced membrane tension built up during adhesion. These results underscore the role of membranes in the generation of mechanical stresses on cellular length scales and that the modulation of hydrostatic pressure due to membrane tension and adhesion can be channelled to perform mechanical work on the environment.

  17. Medication error report: Intrathecal administration of labetalol during obstetric anesthesia

    PubMed Central

    Laha, Baisakhi; Hazra, Avijit

    2015-01-01

    Labetalol, a combined alfa and beta-adrenergic receptor antagonist, is used as an antihypertensive drug. We report a case of an acute rise in blood pressure and lower limb pain due to the inadvertent intrathecal administration of labetalol, mistaking it for bupivacaine, during obstetric anesthesia. The situation was rescued by converting to general anesthesia. The cesarean delivery was uneventful, and mother as well as newborn child showed no ill-effect. This particular medication error was attributable to a failure on the part of the doctors administering the injection to read and cross-check medication labels and the practice of keeping multiple injections together. In the absence of an organized medication error reporting system and action on that basis, such events may recur in future. PMID:26288484

  18. Nanoparticle Stabilized Liposomes for Acne Therapy

    NASA Astrophysics Data System (ADS)

    Fu, Victoria

    Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

  19. Biophysical studies on chitosan-coated liposomes.

    PubMed

    Mady, Mohsen M; Darwish, Mirhane M; Khalil, Safaa; Khalil, Wafaa M

    2009-10-01

    Liposomes have been used as delivery vehicles for stabilizing drugs, overcoming barriers to cellular and tissue uptake, and for directing their contents toward specific sites in vivo. Chitosan is a biological macromolecule derived from crustacean shells and has several emerging applications in drug development, obesity control, and tissue engineering. In the present work, the interaction between chitosan and dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by transmission electron microscopy (TEM), zeta potential, solubilization using the nonionic detergent octylglucoside (OG), as well as Fourier transform infrared (FTIR) spectroscopy and viscosity measurements. The coating of DPPC liposomes by a chitosan layer was confirmed by electron microscope images and the zeta potential of liposomes. Coating of liposome by chitosan resulted in an increase in liposomal size by addition of a layer of 92 +/- 27.1 nm. The liposomal zeta potential became increasingly positive as chitosan concentration increased from 0.1 to 0.3% w/v, then it held at a relatively constant value. The amount of detergent needed to completely solubilize the liposomal membrane was increased after coating of liposomes with chitosan, indicating an increased membrane resistance to the detergent and hence a change in the natural membrane permeation properties. In the analysis of FTIR spectra of DPPC, the symmetric and antisymmetric CH(2) (at 2,800-3,000 cm(-1)) bands and the C=O (at 1,740 cm(-1)) stretching band were investigated in the absence and presence of the chitosan. It was concluded that appropriate combining of the liposomal and chitosan characteristics might be utilized for the improvement of the therapeutic efficacy of liposomes as a drug delivery system. PMID:19649627

  20. The safety of baclofen in pregnancy: intrathecal therapy in multiple sclerosis.

    PubMed

    Dalton, Catherine M; Keenan, Elizabeth; Jarrett, Louise; Buckley, Lisa; Stevenson, Valerie L

    2008-05-01

    Intrathecal baclofen is a GABA-receptor agonist and one of the mainstay treatments of severe spasticity due to multiple sclerosis (MS). The authors report a case on the use of intrathecal baclofen administered using a Medtronic Synchromed II infusion pump. A healthy male infant (2.68 kg, Apgars 9 and 10) was born at 36 weeks gestation by cesarean section, under general anesthetic. This is the fifth reported case of intrathecal baclofen administered during pregnancy and adds to the knowledge that thus far it is relatively safe in pregnancy and may in fact be safer for the infant than oral baclofen. This is the first case report of the use of intrathecal baclofen in pregnancy and MS. PMID:18562512

  1. Sexual Dysfunction Associated With Intrathecal Baclofen Use: A Report of Two Cases

    PubMed Central

    Saval, April; Chiodo, Anthony E

    2008-01-01

    Background/Objective: Intrathecal baclofen is considered standard treatment for severe spasticity of spinal cord and cerebral origin. Recognized side effects include fatigue and constipation. There are few reported findings of sexual dysfunction in men and none in women. Methods: Two case reports. Results: A male and a female patient with spasticity treated with intrathecal baclofen were recognized to have sexual dysfunction side effects from treatment. On reduction of the intrathecal baclofen dose, complete return to baseline sexual function was achieved for both subjects. Conclusions: Intrathecal baclofen can impair sexual function and ejaculation in some patients. Clinicians should be aware of this risk and ask about it during routine clinic follow-up for spasticity. Dosing adjustments need to be considered in these patients. PMID:18533420

  2. Depression, night terrors, and insomnia associated with long-term intrathecal clonidine therapy.

    PubMed

    Bevacqua, Brian K; Fattouh, Maher; Backonja, Misha

    2007-03-01

    Intraspinal clonidine is an effective adjunct to intrathecal/epidural opioid administration. We report a case of neuropathic pain treated with intraspinal analgesics in which depression, insomnia, and night terrors developed in association with intraspinal clonidine. PMID:17305677

  3. Development of the Liposomes Entrapped Ultrasound Imaging Gas (``Bubble Liposomes'') as Novel Gene Delivery Carriers

    NASA Astrophysics Data System (ADS)

    Suzuki, Ryo; Tanaka, Kumiko; Sawamura, Kaori; Takizawa, Tomoko; Utoguchi, Naoki; Negishi, Yoichi; Hagisawa, Kohsuke; Nishioka, Toshihiko; Maruyama, Kazuo

    2006-05-01

    Recently, microbubbles and ultrasound have been investigated with a view to improving the transfection efficiency of nonviral delivery systems for gene by cavitation. However, microbubbles had some problems in terms of stability and targeting ability. To solve these problems, we paid attention to liposomes that had many advantages such as stable and safe in vivo and easy to modify targeting ligand. Previously, we have represented that liposomes are good drug and gene delivery carriers. In addition, we developed that the liposomes ("Bubble liposomes") were entrapped with perfluoropropane known as ultrasound imaging gas. In this study, we assessed about feasibility of "Bubble liposomes" as gene delivery tool utilized cavitation by ultrasound irradiation. "Bubble liposomes" could effectively deliver plasmid DNA to cells by combination of ultrasound irradiation without cyototoxicity. This result suggested that "Bubble liposomes" might be a new class of tool for gene delivery.

  4. Compartmental Intrathecal Radioimmunotherapy: Results for Treatment for Metastatic CNS Neuroblastoma

    PubMed Central

    Kramer, Kim; Kushner, Brian H.; Modak, Shakeel; Pandit-Taskar, Neeta; Smith-Jones, Peter; Zanzonico, Pat; Humm, John L.; Xu, Hong; Wolden, Suzanne L.; Souweidane, Mark M.; Larson, Steven M.; Cheung, Nai-Kong V.

    2012-01-01

    Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. 21 patients treated for recurrent neuroblastoma metastatic to the CNS received a cRIT-containing salvage regimen incorporating intrathecal 131I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n=5), and biochemical hypothyroidism (n=5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life. PMID:19890606

  5. Crimson carrier, a long-acting contrast agent for in vivo near-infrared imaging of injured and diseased muscle.

    PubMed

    Prajapati, Suresh I; Martinez, Carlo O; Abraham, Jinu; McCleish, Amanda T; Michalek, Joel E; McManus, Linda M; Rubin, Brian P; Shireman, Paula K; Keller, Charles

    2010-08-01

    The near-infrared wavelengths (700-900 nm) are the most suitable optical window for light penetration and deep tissue imaging in small animals. Herein we report a near-infrared fluorescent contrast agent, crimson carrier, which acts as a blood pool contrast agent to detect and quantify injury and disease in live animals. After determining the excitation-emission spectra and pharmacokinetics, crimson carrier was injected into myoinjured mice to monitor their recovery. Crimson carrier was also used to image transgenic mice with spontaneous tumors. Crimson carrier has maximal excitation and emission wavelengths of 745 nm and 820 nm, respectively. Elimination occurs predominantly via urinary excretion. We demonstrate the utility of this contrast agent for serial imaging of traumatized muscle as well as muscle tumors. The unique long-acting pharmacokinetics and urinary excretion route characteristics make crimson carrier a contrast agent of choice for the visualization of tumors and injured muscle or other tissues in live animal studies. PMID:20544935

  6. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders

    PubMed Central

    Black, Kirsten I.; Day, Carolyn A.

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID:27199563

  7. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days. PMID:27468018

  8. FDA's recommendations on the use of long-acting {beta}2 agonists in the management of asthma.

    PubMed

    Robinson, Christie A

    2010-10-01

    The revised labeling for long-acting β(2) agonists (LABAs) by the Food and Drug Administration (FDA) is controversial and in part is inconsistent with the 2007 National Asthma Education and Prevention Program asthma guidelines. Two large randomized controlled studies, the Serevent Nationwide Surveillance (SNS) study and the Salmeterol Multicenter Asthma Research Trial (SMART), and a 2008 meta-analysis conducted by the FDA were the main sources of information used to determine the label changes. A paucity of large, well-designed, controlled, prospective studies evaluating the asthma-related risks associated with LABAs makes it difficult to reach a consensus regarding how best to use LABAs in patients with asthma. PMID:20841520

  9. Short- and long-term effect of a long-acting somatostatin analogue, lanreotide (SR-L) on metastatic gastrinoma.

    PubMed

    Gaztambide, S; Vazquez, J A

    1999-02-01

    Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazol are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects. PMID:10195383

  10. [Efficiency of a pharmaceutical care program for long-acting parenteral antipsychotics in the health area of Santiago de Compostela].

    PubMed

    Vázquez-Mourelle, Raquel; Parrondo, Carmen Durán; López-Pardo Pardo, Estrella; Carracedo-Martínez, Eduardo

    2016-01-01

    In the healthcare area of Santiago de Compostela (Spain), the therapeutic subgroup "other antipsychotics" represented the fifth largest outpatient expenditure in 2013. More than half of this expenditure corresponded to long-acting parenteral forms of paliperidone and risperidone. Over a 12-month period, the implementation of a pharmaceutical care program based on process management and coordination of actions between health professionals in both levels of care represented savings of € 636,391.01 for the organization and a direct saving of € 16,767.36 and 9,008 trips to the pharmacy for patients. This study shows the efficiency of the program, which was facilitated by its situation in an area of integrated management and the use the unified medical records and electronic prescription, elements that will enable the future implementation of similar programmes. The new registries and healthcare interventions will allow reliable evaluation of their effectiveness in terms of treatment adherence, relapses and hospitalisations. PMID:26627381