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Preparation and evaluation of a sustained morphine delivery system in rats.

A new drug delivery system to induce physical dependence to morphine in rats is described. The device consists of a silicone polymer containing a water soluble "carrier" material, sodium alginate, which swells on contact with moisture to release the drug. The silicone or silastic pellets formulated to contain morphine sulfate are very easily prepared and the advantages over existing methods to induce physical dependence to morphine are discussed. In addition, a comparison of the percent of drug released and withdrawal intensities in rats was made with a silastic-morphine sulfate pellet, silastic-morphine base pellet and a microcrystalline cellulose-morphine base pellet.

Animals

Turnip Mosaic Virus-Based gRNA Delivery System for Plant Genome Editing.

Plant virus-based gRNA delivery systems offer a rapid alternative to stable transformation for CRISPR-mediated genome editing, but potyvirus-based platforms in Cas9-expressing plants are still underexplored. Here, we developed a turnip mosaic virus (TuMV)-based system for gRNA delivery in Cas9-expressing Nicotiana benthamiana and tested whether Csy4-mediated gRNA processing could improve editing efficiency. A TuMV construct carrying a gRNA targeting PHYTOENE DESATURASE (NbPDS) induced detectable editing in both infiltrated and systemic tissues, although editing frequencies were low. Incorporation of the bacterial endoribonuclease Csy4 increased editing efficiencies in the two NbPDS genes, raising editing in infiltrated leaves to 7.1%-13.8% for NbPDSa and 7.6%-23.0% for NbPDSb, whereas lower but reproducible editing was detectable in systemic leaves. The TuMV-Csy4 platform also supported editing of a second endogenous target, MAGNESIUM CHELATASE SUBUNIT H (NbChlH), and enabled multiplex editing of NbPDS and NbChlH regardless of guide order. Editing efficiencies were consistently higher in infiltrated leaves than in systemic leaves, and no visible photobleaching or chlorosis was observed in systemic tissues despite confirmed molecular editing. To assess the potential for heritable editing, a tRNAIle mobility element was fused to the NbPDS gRNA. Although this construct increased somatic editing, no albino progeny were recovered after screening approximately 20,000 seedlings, demonstrating that heritable editing was not achieved under these conditions or did not result in mutations in all copies of the two NbPDS genes. Together, these results establish TuMV as a platform for Cas9-based gRNA delivery and show that Csy4-mediated processing improves editing efficiency, supports multiplex targeting, and demonstrates the feasibility of potyvirus-based genome editing systems in plants.

genome editing platform

Drug delivery systems for topical ophthalmic medication.

Two new topical ophthalmic delivery systems are described. The modes of delivery were compared with conventionally administered eyedrops on the basis of intraocular pressure lowering effect, dependability in delivery of prescribed dosage, and patient acceptance of the system. Pilocarpine delivered by each of the systems was found to control IOP as well as conventional pilocarpine drops. Although some patients took a longer time than others to adjust to a new mode of delivery, patient acceptance of the systems was high.

Administration, Topical

An evaluation of IUD insertion by a non-clinical delivery system.

To evaluate the safety, effectiveness, side-effects, and continuation rate associated with non-clinical IUD insertion compared to IUD insertion in routine clinical facilities, a cohort comparative study was done on two groups of IUD users self-selected for either the non-clinical or clinical delivery system in Yogyakarta Special Area Province. During the months of January to March 1985, 454 non-clinical and 625 clinical acceptors were recruited into this study. However, only 414 non-clinical and 605 clinical acceptors fulfilled the inclusion criteria and were included in the analysis. Bleeding and pain were the most common side-effects reported by acceptors. The frequency of bleeding was higher in the non-clinical group than in the clinical group. However, the difference was a not statistically significant relative risk (RR) of 1.09 (0.8-1.4) to 1.2 (0.9-1.5). Severe menstrual blood loss mostly occurred in the first three months after insertion and then declined in the rest of the year in both groups. The frequency of pain was not clearly different between the two groups during the whole year, with RR 0.8 (0.5-1.3) to 1.3 (0.8-2.0). The actual number of pregnancies was very small and the difference was not statistically significant (p = 0.375). The 12-month expulsion rates were 7.22 per 100 IUD users for the non-clinical group and 7.00 for the clinical group. The difference was not statistically significant (p = 0.660). The cumulative probability of women who were still using IUDs at 12 months was 89.7% and 89.1% for the non-clinical and clinical groups, respectively. The non-clinical delivery system seemed to be responsive to an unmet demand for family planning among women with lower educational background compared with those in the clinical setting service. While the characteristics of a population obviously influence the contraceptive behavior, this study shows that the non-clinical delivery system family planning method provides a similarly efficacious and safe service to the usual clinical system.

Cohort Studies

An analysis of the processing of patients in a rural medical care delivery system.

A study of the processing of patients at the rural clinic of a medical care delivery system was done to describe quantitatively the movement of patients from their arrival to their departure. The data collected provided a statistical summary of the sequence and duration of observed events in the medical care process as they related to the patients. An analysis of 485 patients visits that were observed on 60 random days during a 12-month period showed that patient arrival rates were generally higher during the morning. The average visit lasted 74 minutes; 94 percent of this time was spent in the waiting and examination rooms. The period that that the patient spent unattended by clinic personnel represented three-fourths of the average patient's total time in the delivery system. Data analysis indicated that if patients were admitted to an unoccupied examination room as soon as possible after their arrival and if standing orders for the family nurse practitioner were expanded, a significant reduction would occur in the average patient's unattended visit time.

Appointments and Schedules

Evaluation of an ambulatory medical-care delivery system.

We designed a medical-care-delivery system specifically to relieve the impaired access to care that has invariably assompanied the elimination of personal fees by prepaid plans, Medicare and other third-party payment plans. The solution involved the entry of patients through a paramedically staffed health-evaluation servece that effectively separated patients into three basic health-status groups-the well and worried well (68.4 per cent); the asymptomatic sick (3.9 per cent); and the sick (27.7 per cent)--a process that permitted matching the needs of each group with appropriate services. The system achieved increased physician accessibility to new patients by 20 times, reduced the waiting time for new appointments from six to eight weeks to a day or two, saved physician time and costs for entry work to a day or two, saved physician time and costs for entry work-up by 70 to 80 per cent reduced total resources used throughout the year by +32,550 per 1000 entrants, and proved very satisfactory to patients and generally so to staff.

Ambulatory Care

Bacteriological and clinical evaluation of different dialysate delivery systems.

In the period 1964-74 four different dialysate delivery systems have been used in our department. 1) Central mixing of dialysate using tap water and a dialysate delivery line with "dead ends" resulting in stagnant dialysate. 2) Central mixing of dialysate with cold distilled water, otherwise equal to system 1. 3) Local mixing of dialysate with cold distilled water, delivered through a line with "dead ends" resulting in stagnant water. 4) Local mixing of dialysate with distilled water, cooled to 25 degrees C just prior to use, reduced "dead ends" and monitored constant overflow to drain through the water supply line. The bacterial contamination of the four systems was examined and related to the clinical occurrence of pyrogenic and other reactions. An improvement was noted with the change from central to local mixing of dialysate (system 3) but complete sterility and virtual freedom from clinical reactions were first obtained in system 4. It is concluded that the use of sterile or near sterile dialysate is recommendable.

Bacterial Infections

Planning health care delivery systems.

The increasing concern and interest in the health delivery system in the United States has placed the health system planners in a difficult position. They are inadequately prepared, in many cases, to deal with the management techniques that have been designed for use with system problems. This situation has been compounded by the failure, until recently, of educational programs to train new health professionals in these techniques. Computer simulation is a technique that allows the planners dynamic feedback on his proposed plans. This same technique provides the planning student with a better understanding of the systems planning process.

Computers

Establishment of a cBSA-mediated miRNA delivery system in Camellia sinensis and functional validation of the Cs-miR163/CsSK1 module in cold stress response.

Cold stress severely limits tea (Camellia sinensis) yield and quality. MicroRNAs (miRNAs) are key post-transcriptional regulators of plant cold responses; however, in vivo functional validation in tea plants is hindered by the lack of efficient genetic transformation and nucleic acid delivery systems. In this study, a cationized bovine serum albumin (cBSA)-mediated miRNA delivery system was established in tea plants. The cold-responsive miRNA Cs-miR163 and its target gene CsSK1 (a negative regulator of cold tolerance) were used as a model. Direct cleavage of CsSK1 mRNA by Cs-miR163 was confirmed by 5' RLM-RACE and GUS transient expression assays, and enhanced cold tolerance was demonstrated in Arabidopsis overexpression lines. The cBSA preparation protocol was optimized, yielding stable cBSA/miRNA complexes with high protective capacity across temperatures of 15-35 °C and pH 4.5-7.2. Delivery parameters were systematically evaluated; optimal conditions were determined as 2 mg/mL cBSA with 10 nM miRNA and solution uptake into 3-cm cuttings for 5 days, enhancing miRNA delivery efficiency by approximately 48-fold. Transmission electron microscopy provided direct ultrastructural evidence that cBSA/miRNA nanocomplexes are internalized into tea plant cells via adsorptive-mediated endocytosis involving electrostatic membrane adsorption, membrane invagination, and cytoplasmic release. Under optimized conditions, cBSA-mediated delivery of Cs-miR163 silenced CsSK1 expression by approximately 72%, reduced relative electrolyte leakage and ROS accumulation, and markedly enhanced cold tolerance. The regulatory role of the Cs-miR163/CsSK1 module was clarified, and the established system provides a promising strategy for functional genomics in woody plants that warrants further testing in additional species and tissues.

Camellia sinensis

The hazards of bulk oxygen delivery systems.

Many hospitals throughout the world obtain oxygen from a supply of bulk liquid oxygen which is delivered throughout the hospital via pipelines. An incident in which, through a series of malfunctions, dangerously high pressure developed in the hospital oxygen pipeline is described. The oxygen delivery systen described lacked a relief valve to vent excessive pressures. In North America such a relief valve is required on all oxygen delivery systems. An alarm system is also required which detects rises in pipeline pressures. Regulations in the U.K. do not provide for pressure-relief valves on liquid oxygen pipeline systems. In the U.K. there is also no regulation on alarms to warn of high pipeline pressures. High-pressure accidents are a real threat to patients and hospital staff unless proper safeguards are built into oxygen delivery systems.

Accident Prevention

Bulk oxygen and nitrous oxide delivery systems: design and dangers.

A survey of hospitals with anesthesia residency training programs was undertaken to determine the frequency and types of complications encountered with the use of bulk supplies of oxygen and nitrous oxide. Of the responding hospitals, 98 per cent dispense oxygen from a central source and 80 per cent dispense nitrous oxide from a central source. Nearly a third of the hospitals responding reported the occurrence of serious or potentially serious accidents related to their bulk gas delivery systems. In three instances accidents resulted in patient deaths. More than half of the reported incidents were decreases in oxygen pipeline pressure, often resulting in insufficient delivery of oxygen for clinical use. Most complications related to pipeline accidents could have been prevented by observance of National Fire Protection Association regulations. Anesthesiologists should be familiar with these regulations and should understand the designs of gas delivery systems in their institutions.

Equipment and Supplies, Hospital

Patient and nurse evaluation of patient-controlled analgesia delivery systems for postoperative pain management.

Five different patient-controlled analgesia (PCA) delivery systems were evaluated for the treatment of acute postoperative pain in 423 patients undergoing elective operations at a large tertiary care hospital. The PCA trial was conducted on four different postsurgical wards over a 5-mo period. All five devices were utilized on each ward for a 1-mo period. According to the nurses, the mean time (+/- SD) required to become comfortable using the Pharmacia Deltec CADD-PCA was significantly longer (50 +/- 37 min) than that using the Abbott Lifecare Plus (19 +/- 17 min), Bard PCA I (17 +/- 14 min), IVAC PCA (17 +/- 14 min), or Baxter PCA Infusor (7 +/- 8 min). With respect to ease of documentation by the nursing staff, the Baxter device was superior to the Pharmacia device. Similarly, mechanical problems were less frequent with the Baxter (6%) compared with the Pharmacia device (71%). The patients felt that the nurses were more comfortable using the Baxter device than the Pharmacia device. The patients also found the Baxter device easier to use, especially at night, and the least likely to interfere with ambulation. In conclusion, 80% of the nurses at this teaching center preferred the Baxter PCA Infusor over four widely used electronic PCA devices for the management of acute postoperative pain. The Pharmacia device was felt by the nurses to be less user friendly than the other programmable PCA devices used in this trial. Of the electronic devices we studied, the Bard and IVAC devices were the most cost-effective.

Aged

Patterns of ambulatory health care in five different delivery systems.

Few empirical investigations permit systematic comparison of the impact of widely-varying delivery systems within a single population sample. This study provides such a comparison, describing patterns of ambulatory care among patients using five different systems in Washington, D.C. as a regular source of health care: solo practice, fee-for-service group practice, prepaid group practice, public clinics, and hospital outpatient departments or emergency rooms. Comparisons are adjusted statistically to account for major patient group variations, and the results reveal substantial differences among the five systems. Sources used primarily by the poor--hospital outpatient departments, emergency rooms, and public clinics--contained important structural and financial barriers, and had the lowest rates of patient-initiated use. The prepaid system, in contrast, maximized patient's access to both preventive care and symptomatic care, and did not seem to inhibit physician-controlled follow-up care. The results suggest some perverse effects of fee-for-service payment: patients, especially poor patients, appeared to be deterred from seeking preventive and symptomatic care, while physicians were encouraged to expand follow-up services. Moreover, services in fee-for-service systems were distributed less equitably relative to both income and medical need than in the prepaid system. These findings have direct implications for policy decisions concerning organizational and financial arrangements for the delivery of ambulatory care.

Adult

Analysis of theoretical behavior of a proposed zero-order drug delivery system.

An analysis of the theoretical behavior of a proposed zero-order drug delivery system is presented. Equations describing drug release with time are developed using a physically realistic model. The theory agrees well with experimental data and indicates that drug release from the device is nearly, although not rigorously, zero order.

Delayed-Action Preparations

['Our future selves'. Comments on "Human services and delivery systems'].

A description is given of the recommended research topics on Human Services and Delivery Systems for the Aging. Fifteen different fields of research attention are described. It is stated that there is a lack of a frame of reference for the different attention fields. This frame of reference is necessary for a more systematic approach towards the age specific problems and the age specific services, needed to solve those problems. The systematic approach can be found in a three-dimensional scheme in which the fifteen attention fields have their logical place. The recommanded research topics have to be assessed in this frame: 1. Socio-cultural aspects. Culture, religion, ethics, communication, education, recreation, civic participation. 2. Socio-economic aspects. Economic support, employment, legal services, commerce. 3. Physical environment. Physical Environment, nutrition, transportation. 4. Human environment. This aspect is not mentioned in the report. 5. Psychological aspects. 6. Physical aspects. These aspects are not explicitly mentioned in the report, but implicitly in the chapter about Health. Some of the recommendations are also relevant for the situation in the Netherlands. The recommended research on the health care system is critisized, because the items are too complex. For the Netherlands it is more worthwhile to do fundamental research on the age-specific vulnerability in relation to social, psychological and physical aspects. The results of that research can be used for a reconstruction of the whole health care system for the aged.

Aged

Electric shock delivery system for rhesus monkeys: its effect on escape responding.

The present experiment evaluated a simple chronic electric shock delivery system for rhesus monkeys restrained by a harness and arm arrangement used in experiments involving intravenous drug delivery. Electric shock was delivered via two small electrodes surgically implanted in the lumbar muscle. During experimental sessions, responding on a fixed-ratio 10 schedule terminated the delivery of a train of 100 electric shock pulses and produced a 3 min timeout. A maximum of 19 trials were possible during each daily session. Overall rate of responding increased as electric shock intensity was increased from 0 to 4 mA and the characteristics of responding were similar to previous studies using other systems and species. The results demonstrate that electric shock delivered by the present system is a negative reinforcer. In addition, the system is easy to implant, causes little tissue damage, relatively long-lasting and can be used in experimental situations which involve responding maintained by intravenous drug delivery in rhesus monkeys.

Animals

Short dialysis with a polyacrylonitrilmembrane (RP 6) without the use of a closed recirculating dialyzate delivery system.

Because of excessive eltrafiltration (UF), the RP 6 dialyzer requires a closed recirculating dialyzate delivery system. The purpose of this study is to present the characteristics of the RP 6 dialyzer on a single needle system which programs the UF rate of this dialyzer. The single needle system consists of one blood pu-mp and two roller pump heads, switched on and off at preselected maximum and minimum out let pressures (OP). It is possible to decrease the UF rate by lowering the OP in the bubble trap chamber. By varying OP from 0 to 100 mm Hg, we obtained an UF rate in vitro of 6.5 ml per minute. The clearance values, in ml/min, obtained at OP 0 to -100 NN Hg, QB 300 and QD 500 are (in ml/min): urea: 160.0, creatinine: 145.0, sucrose-C14: 105.4, sodiumiothalamate-i125: 79.9, cyanocobalamin-co58: 73.7 and inulin-3H: 40.7. The priming volume (corn-oil) at OP 0 to -100 MM Hg, QB 250, QD 500 varies between 140 ml (at the minimum OP) and 150 ml (at the maximum OP). We performed 370 dialyses. The dialysis runs were well tolerated: moderate hypotension occurred in 4% and cramps in 1.6% of the dialyses. In most cases no fluid perfusion was necessary. The residual blood volume (Technetium99m) is estimated at 8.2 ml(n equale 11).

Acrylic Resins