W. Samuel. University of South Carolina, Spartanburg.

Process improvement approach to tracking and trending computerized order entry medication variances using a formal error classification system buy silvitra 120 mg without a prescription. Process improvement using clinical decision support for high-risk medications based on medication variance reporting cheap silvitra 120 mg fast delivery. Collaborative pharmacist and nurse before/after study to evaluate patient safety using electronically standardized admission and discharge medication reconciliation in a tertiary care hospital. The treatment of hyperglycaemia in critically ill patients: comparison of standard protocol and computer algorithm. Streamlining the workflow process of a hospital pharmacy department implementation of a computerized physician order entry system. Patient acceptance of educational voice messages: A review of controlled clinical studies. Assessing the accuracy of a computerized decision support system for digoxin dosing in primary care: an observational study. Adherence to continuous quality improvement principles lead to reduced harmful medication errors. Bedside bar code charting, smart pump dose mode programming and computer assisted physician order entry system utilization monitoring and quality improvement lead to reduced harmful medication errors. Antimicrobial stewardship programs: Role in optimizing infectious disease outcomes. System for exchanging information among pharmacists in different practice environments. Medication errors in inpatient pharmacy operations and technologies for improvement. Pharmacovigilance in New Zealand: The role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use. Evidence-based information technology: Concept for rational information processing in the health care system. An interoperability infrastructure with portable prescription for improving patient safety - the framework of a national standard in Taiwan. Proceedings - the Annual Symposium on Computer Applications in Medical Care 1994;836-40. Decision support for medication use in an inpatient physician order entry application and a pharmacy application. Improving response to critical laboratory results with automation: results of a randomized controlled trial. Patient safety and computerized medication ordering at Brigham and Women’s Hospital. Medication-related clinical decision support in computerized provider order entry systems: a review. A virtual reality apartment as a measure of medication management skills in patients with schizophrenia: a pilot study. Predicting changes in workflow resulting from healthcare information systems: ensuring the safety of healthcare. Using a low-cost simulation approach for assessing the impact of a medication administration system on workflow. Using simulation methods to analyze and predict changes in workflow and potential problems in the use of a bar-coding medication order entry system. Project for surveillance of antimicrobial therapy advances rational prescriptions. Improving adherence to asthma clinical guidelines and discharge documentation from emergency departments: Implementation of a dynamic and integrated electronic decision support system. Transition from the traditional pharmacy model toward pharmaceutical care using automation. Decision support for evidence-based public health practice and policy development in the global south. Invited Paper for the Rockefeller Foundation’s Making the eHealth Connection: Global Partnerships, Local Solutions Meeting. The role of information technology in a study on antithrombotic-related bleeding events The University of UtahEditor. Implementation of computerized information systems in the pharmaceutical technology department. Design of a graphical and interactive interface for facilitating access to drug contraindications, cautions for use, interactions and adverse effects. Health information technology for improving quality of care in primary care settings. A simple, live, cost-effective electronic tracking system for aseptic preparations: Improving communication and reducing disruptions. Improved perioperative antibiotic use and reduced surgical wound infections through use of computer decision analysis. Medication reconciliation: From admission to discharge using electronically generated medication forms from a clinical information system.

It is important to inform the patient that purchase 120 mg silvitra visa, although the operation is safe buy silvitra 120 mg low cost, complications and rare deaths have occurred with donation. Currently, donation in this country is based solely on an altruistic basis, and paid donation is prohibited. Surgical Techniques The kidney transplant operation is well described in Chapter 65, “Kidney Transplantation and Dialysis Access,” in Surgery: Basic Science and Clinical Evidence, edited by J. An important point to note is the difference between placing a kidney obtained from a cadaver donor and placing a kidney obtained from a live donor. During the procurement of a kidney from a cadaveric donor, a cuff of vena cava and aorta can be left on the renal vein and artery, respec- tively. The renal vein anastomosis actually is sewn between the cuff of the vena cava and recipient’s external iliac vein in an end-to-side fashion. This anastomosis can be done without the worry of tearing the thin wall of the right renal vein. Large hemostatic bites of the vena cava may be taken without concern for narrowing the anastomosis. Having a cuff of aorta allows for a single anastomosis even in the presence of multiple renal arteries. Once again, with a large cuff, the surgeon need not be concerned with narrowing the renal artery anastomosis. In kidneys obtained from live donors, the renal artery may be sewn to the external iliac artery in an end-to-side fashion or to the internal iliac artery in an end-to-end fashion. The left kidney often is the preferred kidney, especially from a live donor, as the left renal vein is considerably longer and thicker-walled than the right renal vein. Occa- sionally, the recipient’s internal iliac vein is divided to enable the exter- nal iliac vein to be moved more anteriorly and out of the pelvis. If the kidney from a live donor has two arteries, they may both be sewn directly into the external iliac artery. The incidence of renal artery steno- sis may be reduced by the uses of an aortic punch biopsy. More com- monly, the smaller of the two arteries is sewn into the larger main renal artery in an end-to-side fashion under ice on the back table. The kidney is then placed within the recipient, and a single anastomosis between the main renal artery and the recipient iliac artery (external or internal) is performed. Vascular thrombosis of the artery and vein are rare events: arterial thrombosis occurs less than 1%, and venous thrombo- sis occurs less than 2%. Posttransplant Period The differential of an increasing serum creatinine is influenced sig- nificantly by the amount of time from the day of the transplant to the increase in serum creatinine (Fig. Three different time periods can be created based on the most likely cause for an increasing serum creatinine post–kidney transplant: the early period, the intermediate period, and the late period. Throughout the posttransplant period, a thorough history and a thorough physical exam help narrow the differential diagnosis of a rising serum creatinine. Duplex ultrasound identifies fluid col- lection around the kidney and reveals the status of blood flow through the artery and vein. A renal scan often is helpful in identifying changes in renal flow and urinary leaks, and a kidney biopsy is needed to make a definitive diagnosis of rejection. These tests are used routinely in sorting out the correct etiology for the recipient of a renal allograft who presents with a rising serum creatinine. The following sections describe the most likely causes of deteriora- tion in renal function, based on time from transplant to change in func- tion, and focus the history and physical exam on the most pertinent facts (Fig. The Early Period In the early postoperative period, day 0 to day 7, the differential diag- nosis can be broken down into immunologic causes, technical causes, 712 D. Immunologic Causes Hyperacute rejection has become a rare event, as the ability to detect preformed antibodies prior to the transplant has improved. Hyper- acute rejection derives from antibodies in the recipient’s serum directed against the donor’s antigens. These preformed antibodies bind to the donor tissues, activating the complement cascade, which leads to imme- diate graft thrombosis. The two methods for screening for donor-specific antibodies are lymphocytic crossmatch and flow cytometric studies. The level of preformed antibodies is too low to be detected by the current screening test, but it quickly rises with stimulation by exposure to the new donor antigen. Clinically, the kidney often is functioning; however, urine output acutely falls off, and serum creatinine rises. Patients at risk for hyperacute rejection or early vascular rejection have been exposed previously to antigens. Transplantation of the Kidney 713 checked on a monthly basis for antibodies against a panel of known human antigens.

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Physiological changes in the pH of the vaginal fluids can also result in fluctuations in vaginal bioavailability buy silvitra 120 mg visa. For example purchase silvitra 120mg on line, using casein as a substrate, the proteolytic activity determined in a 10% homogenate of rat vaginal membrane was found to be less than that in the small intestine. The influence of the ovarian cycle on protease activity in the vagina has also been demonstrated. For example, the trypsin-like activity in rat vaginal smears was found to be maximal at proestrus. The activity of β-glucuronidase, acid phosphatase, alkaline phosphatase, and esterase all vary in the vaginal tissue of premenopausal and postmenopausal women. As described in general terms for the transepithelial absorption of drugs at any site (Section 1. In contrast, lipid-soluble drugs are usually absorbed transcellularly, by passive diffusion through the epithelium, down a concentration gradient according to Fick’s Law (Section 1. Drug diffusion rates correlate with their lipid/water diffusion coefficients and are inversely related to their molecular size (Section 1. However, these general observations do not take into account the cyclical changes in the vaginal epithelium, which exert profound effects on vaginal absorption, especially for hydrophilic compounds. The permeability coefficient for the vaginal membrane (P ) is equal to the sum of the permeability coefficientm through the lipid pathway (P ) and the pore pathway (P ):l p P =P +Pm l p For lipophilic drugs, the contribution of the pore pathway to transport is negligible and drug absorption occurs transcellularly, via passive diffusion through the epithelial cells. For example, it has been shown that increasing the chain length (increasing the lipophilicity) of aliphatic alcohols and carboxylic acids results in an increased rate of vaginal absorption. In contrast, for hydrophilic drugs, the pore pathway constitutes the major absorption pathway and this pathway is influenced by the physiological changes in the thickness of the vaginal epithelium and also in the number of intercellular pores and aqueous channels. As described earlier, in rodents, during proestrus and estrus, the epithelium is thick, tightly cohesive and contains a large number of intercellular junctions. However, the metestrous and diestrous phases are characterized by a thinning of the epithelium and a pore- like widening of the intercellular channels. As the vaginal epithelial membrane barrier becomes thin, loose and porous, the permeability is enhanced, particularly to hydrophilic substances. Thus even high molecular 280 weight hydrophilic drugs can be absorbed by the intercellular route during the metestrous and diestrous phases. Several examples of this phenomena are described below: Salicylic acid Vaginal absorption of salicylic acid in different pH buffers has been investigated in rats during proestrus and diestrus. For the unionized, lipophilic form of the drug, the rate of vaginal absorption is rapid and similar for both stages. The unionized, lipophilic form is absorbed via transcellular passive diffusion and thus not affected by the stage of the estrous cycle. However, for the ionized, water-soluble form, a significant difference in the degree of absorption is observed: • proestrus (tight epithelium)=29% absorbed; • diestrus (porous epithelium)=66% absorbed. The hydrophilic form is absorbed mainly through pore-like pathways such as the intercellular channels and thus is highly dependent on the stage of the cycle, with greater absorption occuring when the interceullular channels are wide and porous. The percentage of the dose of phenol red excreted in the urine increased more than an order of magnitude from the proestrous phase (2. Leuprorelin showed similar enhanced absorption during the permeable phase of the estrous cycle (Figure 11. Penicillin In humans high blood levels of penicillin, sufficient to be therapeutic, were demonstrated following insertion of a vaginal suppository near the end of the menstrual cycle and during menopause. In contrast, absorption was shown to be somewhat diminished during estrus and late pregnancy. Vidaribine The permeability coefficients of the hydrophilic antiviral compound vidaribine are 5 to 100 times higher during early diestrus or diestrus than during estrus. These results confirm that the cyclic changes in the reproductive system have profound implications for vaginal drug delivery as: • the vaginal permeability to hydrophilic substances is enhanced during the metestrous and diestrous stages of the estrous cycle, corresponding to the late luteal and early follicular phases of the menstrual cycle; • large fluctuations in absorption occur, depending on the particular stage of the menstrual cycle. Although it is well known that carrier-mediated transport systems exist for di- and tripeptides in the intestine, there is still no evidence for carrier-mediated transport of peptides across the vaginal mucosa, although prostaglandins have been demonstrated to utilize such a mechanism. Although there must be some type of endocytic transport of endogenous peptides into the epithelial cells in order to regulate proliferation, no receptor-mediated or bulk-fluid mechanisms have been reported. Hydrophilic compounds may be absorbed via the paracellular route, moving between the epithelial cells via passive diffusion whereas lipid soluble drugs are usually absorbed transcellularly, at rates which correlate with their lipid/water diffusion coefficients. However, in the vagina these factors must be considered in conjunction with the cyclical changes in the vaginal epithelium. Thus hydrophilic compounds show enhanced absorption during metestrus and diestrus, when the vaginal barrier becomes thin, loose and porous. In addition to physicochemical properties of the drug such as size, pKa, chemical stability etc. Furthermore, peptides and proteins are susceptible to self-association, aggregation or polymerization in the medium due to changes in pH, ionic strength of the medium, or concentration of the substance. It is anticipated that the monomer, oligomer, or aggregated complex may each have a characteristic diffusion and permeation coefficient.

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Inaccurate Splicing After Mutation in a Splice Site I ~-Th~lassemia - l i There are two genes for the beta chain of hemoglobin purchase silvitra 120mg. In ~-thalassemia cheap silvitra 120 mg with amex, there is a deficiency I I of ~-globin protein compared with a-globin. A large number of ~-globin mutations have I I been described, including gene deletions, mutations that slow the transcriptional process, I I and translational defects involving nonsense and frameshift mutations. A 9-month-old infant of Greek descent was brought to the hospital by his parents because he became pale, listless, and frequently irritable. The attending physician noted that the spleen was enlarged and that the infant was severely anemic. It is believed that, similar to, sickle cell anemia and glucose-6-phosphate dehydrogenase deficiency, the abnormality of! Splenomegaly is due to the role of the spleen in clearing damaged red cells from the bloodstream. The excessive activity of the bone marrow produces bone deformities of the face and other areas. The most common treatment is,i blood transfusions every 2-3 weeks, but iron overload is a serious consequence. The expansion of the trinucleotide repeat in the mutant allele can be in has a mean age-of-onset a coding region (Huntington and spinobulbar muscular atrophy) or in an untranslated region of 43-48 years. In these diseases, the number of repeats often appear gradually and worsen increases with successive generations and correlates with increasing severity and decreasing age.. The normal protein contains five adjacent glutamine residues, whereas the I· memory, and hyperreflexia are proteins encoded by the disease-associated alleles have 30 or more adjacent glutamines. The often the first signs, followed long glutamine tract makes the abnormal proteins extremely unstable. Because base pairing is involved, the orientation of this interaction will be complementary and antiparallel. The formation of a peptide bond between the car- boxyl group on one amino acid and the amino group of another is illustrated in Figure 1-4-6. Notice that the peptide bond forms between the carboxyl group of the amino acid (or growing peptide) in the P site and the amino group of the next amino acid in the A site. In eukaryotes, translation and transcription are completely separated in time and space with transcription in the nucleus and translation in the cytoplasm. The process of protein synthesis occurs in three stages: initiation, elongation, and termination (Figure 1-4-8). The large subunit binds to the small subunit, forming the completed initiation complex. There are two important binding sites on the ribosome called the P site and the A site. After formation of the first peptide bond, the P site is a binding site for the growing peptide chain. Elongation Elongation is a three-step cycle that is repeated for each amino acid added to the protein after the initiator methionine. Peptidyl transferase, an enzyme that is part of the large subunit, forms the peptide bond between the new amino acid and the carboxyl end of the growing polypeptide chain. In the translocation step, the ribosome moves exactly three nucleotides (one codon) along the message. Puromycin inhibits both prokaryotic and eukaryotic translation by binding to the A site. Peptidyl transferase attaches the peptide to puromycin, and the peptide with puromycin attached at the C-terminus is released, prematurely terminating chain growth. Generally; four levels of protein shape are dis- The majority of cases of cystic tinguished: fibrosis result from deletion • of phenylalanine at position Primary-sequence of amino acids specified in the gene. An individual protein may contain both types of secondary processing of oligosaccharide structures. Some proteins, like collagen, contain neither but have their own more char- side chains. Tertiary structure also includes the shape of the protein as a whole (globu- rather than being translocated lar, fibrous). Tertiary structures are stabilized by weak bonds (hydrogen, hydrophobic, to the cell membrane. There is a class of spe- I cialized proteins, chaperones, whose function is to assist in this process. Molecular chaperones function in many cell compartments, including the endoplasmic reticulum, where extensive protein synthesis occurs. Proteasomes and Ubiquitin Whenever protein synthesis occurs in a cell, a few copies of a particular protein may not fold correctly. These defective copies are covalently marked for destruction by the addition of mul- tiple copies of ubiquitin. Proteasomes are large, cytoplasmic complexes that have multiple protease activities capable of digesting damaged proteins to peptides, as shown in Figure 1-4-9. Degradation of Misfolded Proteins By Proteasomes Many proteins require signals to ensure delivery to the appropriate organelles.

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