By V. Kafa. University of Houston, Clear Lake. 2018.
The interventions aimed at pharmacists both resulted in 507 significant reductions in inappropriate prescribing purchase midamor 45 mg on line. Raebel and colleagues reported a relative risk reduction of 16 percent inappropriate prescribing for elderly patients buy cheap midamor 45mg on-line, and Humphries et 577 al. Negative results were found by Riggio with longer times to stop heparin treatment in patients experiencing heparin induced thrombocytopenia following implementation of an alert for 100 patients. Time from alert to laboratory test and start of direct thrombin inhibitor treatment did not vary before and after the implementation. We considered positive studies to have at least 50 percent of the outcomes as being significantly impacted by the technology. Under this measure, four of the studies did not show significant impact of the technologies on patient 425,555,685,702 701 outcomes though they tended towards being positive. Balcezak and colleagues found better prescribing of heparin when a computerized nomogram was used by prescribers, but the nomogram was only used for 10 percent of prescriptions written. The highest quality 507 618 612 evidence comes from Raebel, White, and Feldstein and their colleagues who all showed positive, significant impacts of the technologies on narrow therapeutic index drug management. The observational study 564 by Smith and colleagues in 15 primary care clinics to reduce prescribing on nonpreferred drugs in elderly patients showed a significant decrease in exposure of elderly patients to nonpreferred drugs, but no change in nonelderly patients, and a nonsignificant positive trend of preferred drugs in elderly patients. Peterson and colleagues found no change in length of stay or rate of altered status, but a significant reduction in falls (p = 0. Wrona and colleagues found improved respiratory rate in patients on morphine and hydromorphone with order sets outlining monitoring and documentation requirements. Unintended consequences can be minor or major and they can be viewed as being helpful to the installation or detrimental. Because we report only those outcomes that the authors reported as the primary or main findings of the study, this listing of articles on unintended consequences is likely not comprehensive. As in previous sections of this 508 report most of the studies evaluated prescribing. The order communication phase was evaluated in two studies, one 69 15 732 15 observational and one qualitative study. No studies of unintended consequences evaluated the monitoring phase or education and reconciliation. Most of the studies were done at an institution level rather than a patient or 508 provider level. Nurses were evaluated in two studies, and the rest of the studies included a range of clinicians. Raebel and colleagues studied drugs with potential for harm to the fetus in pregnant women (category D and X medications). These unintended consequences were categorized into direct compared with indirect, desirable compared with undesirable, and anticipated compared with unanticipated occurrences. Ash and colleagues contend that most unintended consequences center on errors, security concerns, and issues related to alerts, workflow, ergonomics, interpersonal relations, and reimplementation (e. Because of the seriousness of the implications of this study, many people reviewed this article. New and different types of errors were identified as unintended consequences in three 450,457,503 studies. One study felt that problems with communication 775 would probably lead to errors in medication management, and another study postulated the 734 same increase in errors based on challenges to existing and changing roles. The study of use of inappropriate medications during pregnancy was stopped early because the system was not 70 accurate enough, causing the system to “miss” notification of drugs that should have been alerted 508 and to give alerts that were not needed. Ash and colleagues list 47 types of unintended consequences and Kopppel and 752 colleagues list 22. Ash and colleagues go on to verify that the types of unintended consequences they found were common in institutions outside those that she and her colleagues 777 734,743,752,776,781 775,779 studied. Unintended consequences were related to roles, communication, 752,759,779 workflow alterations or automation of poor existing workflows, inflexibility of the new 743,752,759 752,759,776 480,776,779 system, poor content or poor display of content, alert fatigue, and 779 overdependence on the system. Rather than fix the system, most often workarounds were 732,743 instituted by clinical staff. Discuss gaps in research, including specific areas that should be addressed and suggest possible public and private organizational types to perform the research and/or analysis. Where an issue is more strongly associated with a phase we mention the phase or other aspect (e. The literature places a great emphasis on studying the prescribing phase of medication management, with 263 of our included studies falling in that phase (Table 18). We feel that more study should be done on the phases of order communication, dispensing, and administering. Reconciliation of medications is vital, especially at the time of transfer to another health care setting, including transfer to and from home and community.
In the heart generic 45mg midamor mastercard, the gene is also expressed purchase 45mg midamor free shipping, but the transcripts are only 104 kb long. Skeletal Clinical Correlate Muscle Brain Liver Testis Lung Pancreas Heart Fragile X Syndrome Fragile X syndrome is the leading known cause of inherited mental retardation. For example, pre- vious research has suggested that cells from a breast cancer express a variety of genes that are either not expressed or expressed only at a low level in normal cells. The pattern of gene expression (gene expression profiling) may give information about the prognosis for that particular woman, aiding in making choices about the appropriate treatment protocol. Western Blots Western blots separate proteins by gel electrophoresis and use 12sI-labeled probe antibodies to detect the proteins (antigens). Western blots may also be used to identify whether a particular protein is in a cell and therefore represent a way to test for gene expression at the level of translation. This process is repeated for approximately 20 cycles, producing over a million double-stranded copies of the target sequence. Such primers amplify "single-locus" sequences, which are highly polymorphic within the population. Because humans have pairs of chromosomes, each individual will have a maximum of two bands, one from the father and one from the mother. Paternity Testing Are the tested males (Figure 1-7-6) in case 1 and case 2 the fathers of the children? Case 1: The tested male in case 1 may be the father, as he shares a band with the child. We can- not be certain, however, because many other men in the population could have this same band. Matches are required at several different loci to indicate with high probability that a tested male is the father. The wristbands of the two similar-looking infants (A and B) were inadvertently mixed at the pediatric care unit. Parents 1 Parents 2 F1 M1 A B M2 F2 What is the best conclusion from the analysis? Sickle cell anemia is caused by a missense mutation in codon 6 of the ~-globin gene. Which 12-base nucleotide sequence was most likely used as a specific probe complementary to the coding strand of the sickle cell allele? The glucose 6-phosphatase gene is on different chromosomes in the marmoset and in the human. A couple seeks genetic counseling because both the man and the woman (unrelated to each other) are carriers of a mutation causing ~-thalassemia, an autosomal recessive condi- tion. They wish to know whether the fetus in the current pregnancy will have ~-thalassemia. Although unlikely given the situation, another pos- sibility is consistent with the blot. Knowing the son is homozygous for the normal allele, one can conclude that the two restriction fragments shown in his pattern derived from chromosomes without the mutation. The fetus therefore is heterozygous for the mutation and the normal allele of the p-globin gene. The amino acids differ from one another only in the chemical nature of the side chain (R). Classification The amino acids can be classified as either hydrophobic or hydrophilic, depending on the ease with which their side chains interact with water. In general, proteins fold so that amino acids with hydrophobic side chains are in the interior of the molecule where they are protected from water and those with hydrophilic side chains are on the surface. Additional points about some of these amino acids include: Phenylalanine and tyrosine are precursors for catecholamines. The acidic amino acids (aspartic and glutamic acids) have carboxyl groups that are negatively charged, whereas the basic amino acids (lysine, argi- nine, and histidine) have nitrogen atoms that are positively charged. Additional points about some of these amino acids include: • Serine and threonine are sites for O-linked glycosylation of proteins, a posttransla- tional modification that should be associated with the Golgi apparatus. Asparagine is a site for N-linked glycosylation of proteins, a posttranslational modifi- cation that should be associated with the endoplasmic reticulum. Cysteine contains sulfur and can form disulfide bonds to stabilize the shape (tertiary structure) of proteins. He was taken to the hospital, where he was found to have mild anemia, splenomegaly, and rod-shaped crystals in the erythrocytes. To validate the diagnosis, a small aliquot of his blood was subjected to electrophoresis to determine the identity of the hemoglobin in his erythrocytes. After reviewing the data, the physician concluded that he did not have sickle cell anemia, but rather a sickle cell anemia-like hemoglobinopathy with the relatively common mutation of HbC.
Therefore buy 45mg midamor fast delivery, the chance that the two related half first cousins have the same disease gene order midamor 45mg without prescription, is 1/2 X 1/2 X 1/2 X 1/2, or (112)4. The chance that two heterozygous carriers of an auto- somal recessive trait will produce a homozygous affected child is one in 4, or ~. The total probability of these events happening together then is (112)4 X ~, or 1/64. In this example, the disease frequency, q2, is 1/100, and the allele frequency, q, is 1/10, or 0. Using the assumption that the normal allele frequency, p, is about 1 is not necessarily valid. With the application of the Hardy-Weinberg principle to this auto- somal recessive disease, if 1/100 individuals are affected in a population, then q2 = 1/100 and q = 1/10, or 0. These alterations may involve the presence of extra chromosomes or the loss of chromosomes. Chromosome abnormalities are seen in approximately 1 in 150 livd births and are the leading known cause of mental retardation. It is diploid, showing both copies of each autosome, the X and the Y chromo- some. Chromosomes are ordered according to size, with the sex chromosomes (X and Y) placed in the lower right portion of the karyotype. Metaphase chromosomes can be grouped according to size and to the position of the centromere, but accurate identification requires staining with one of a variety of dyes to reveal characteristic banding patterns. Chromosome banding To visualize chromosomes in a karyotype unambiguously, various stains are applied so that banding is evident. G-banding reveals a pattern of light and dark (G-bands) regions that allow chromosomes to be accurately identified in a karyotype. Cytoge~etics Chromosome abnormalities in some cases can be identified visually by looking at the banding pattern, but this technique reveals differences (for instance, larger deletions) only to a resolu- tion of about 4 Mb. Submetacentric chromosomes have the centromere displaced toward one end (for example, chromosome 4). In these chro- mosomes, the p arm contains little genetic information, most of it residing on the q arm. Only the acrocentric chromosomes are involved in Robertsonian translocations, which will be discussed in this chapter. Gametes (sperm and • Triploid (69 chromosomes): egg cells) are euploid cells that have 23 chromosomes (one member of each pair); they are said to be haploid. Most somatic cells are diploid, containing both members of each pair, or 46 rare lethal condition chromosomes. Two types of euploid cells with abnormal numbers of chromosomes are seen in • Tetraploid (92 humans: triploidy and tetraploidy. Triploidy refers to cells that contain three copies of each chromosome (69 total)! Triploidy, which usually occurs as a result of the fertilization of an ovum by two sperm cells, is common at conception, but the vast majority of these conceptions are lost prenatally. These babies have multiple defects of the heart and central nervous system, and they do not survive. Tetraploidy refers to cells that contain four copies of each chromosome (92 total): This lethal condition is much rarer than triploidy among live births: Only a few cases have been described. Aneuploidy - Aneuploidy, a deviation from the euploid number, represents the gain (+) or loss (-) of a spe- cific chromosome. Two major forms of aneuploidy are observed: • Monosomy (loss of a chromosome) • Trisomy (gain of a chromosome) Autosomal aneuploidy Two generalizations are helpful: • All autosomal monosomies are inconsistent with a live birth. Trisomy is the most common genetic cause of spontaneous At least one X chromosome is required for survival. If more than one X chromosome is present, all but one will become a Barr body in each cell. The two important sex chromosome aneuploidies are Turner syndrome and Klinefelter syn- drome. Mosaicism in Turner Edema of wrists and ankles in newborn syndrome is thought to arise Cystic hygroma in utero resulting in excess nuchal skin and "webbed" neck in early embryogenesis by Primary amenorrhea mechanisms that are not Coarctation of the aorta or other congenital heart defect in some cases completely understood. The original cell is diploid for all chromosomes, although only one homolo- gous pair is shown in the figure for simplicity. When fertilization occurs, the conception will be a trisomy 21 with Down syndrome. The other gametes with no copy of chromosome 21 will result in conceptions that are monosomy 21, a condition incompatible with a live birth. In this case, the sister chromatids of a chromosome (for example, chromosome 21) fail to segregate (disjoiri). When fertilization occurs, the conception will be a trisomy 21 with Down syndrome. One gamete has no copy of chromosome 21 and will result in a conception that is a monosomy 21. Clinical Correlate: Maternal Age, Risk of Down Syndrome, and Prenatal Diagnosis Surveys of babies with trisomy 21 show that approximately 90% to 95% of the time, the extra copy of the chromosome is contributed by the mother (similar figures are obtained for trisomies of the 18th I and 13th chromosomes).
Which of the following enzyme deficiencies is most consistent with these observations? Parahemophilia is an autosomal recessive bleeding disorder characterized by a reduced plasma concentration of the Factor V blood coagulation protein cheap midamor 45 mg otc. Deficiency arises from a 12 base-pair deletion in the Factor V gene that impairs the secretion of Factor V by hepa- tocytes and results in an abnormal accumulation of immunoreactive Factor V antigen in the cytoplasm buy 45 mg midamor. Collagen, the most abundant protein in the human body, is present in varying amounts in many tissues. If one wished to compare the collagen content of several tissues, one could measure their content of A. A 6-month-old infant is seen in the emergency room with a fractured rib and subdural hematoma. Respiratory tract infections caused by Pseudomonas aeruginosa are associated with the secretion of exotoxin A by this organism. Stimulation of histamine release 66 meClieal • i I,I The Genetic Code, Mutations, and Translation I: 12. The nucleotide sequences of codons 506-511 in this region of the normal and mutant alleles are compared below. Deletion of a phenylalanine residue causing a change in the C-terminal sequence D. Note release of lysosomal enzymes into serum, which would not be seen in the other deficiencies. Decreased factor V secretion and a corresponding accumulation of cytoplas- mic antigen suggest a defect in the translocation of the nascent protein to the endoplasmic reticulum. Although collagen is also rich in glycine, many other proteins contain significant amounts of glycine. The child has Menkes disease, in which cellular copper transport is abnormal and produces a functional copper deficiency. His fragile bones and blood vessels result from weak, poorly crosslinked connective tissue. Increasing or decreasing the expression of a gene can occur through a variety of mechanisms, but many of the important ones involve regulating the rate of transcription. Other mechanisms are important, and, especially in eukaryotes, gene expression is controlled at multiple levels. An operon is a set of structural genes coding for a group of proteins required for a particular metabolic function along with the regulatory region(s) that controls the expression of the structural genes. The Lactose Operon Lactose The lactose operon (Figure 1-5-1) is a portion of the bacterial chromosome that controls the Lactose synthesis of three enzymes involved in the metabolism of the sugar lactose. Most bacteria carry Permease out glycolysis, a pathway that allows glucose to be metabolized as a carbon and energy source. Bacterium If glucose is unavailable, they can metabolize alternative carbohydrates, but require proteins in addition to those in glycolysis to do so. Lactose, a disaccharide of galactose and glucose, repre- Lactose sents one alternative sugar, and the genes of the lactose operon encode the additional proteins required for its metabolism (Figure 1-5-2). The cell expresses these genes only when lactose is J ~-Galactosidase available and glucose is not. The i gene is constitutively expressed (not regulated); thus, copies of the lac repressor protein are always in the cell. Coordinate Control of the Lactose Operon by Glucose and Lactose Full expression of the lactose operon requires that both mechanisms favor gene expression. Enhancers have the following The Ig heavy chain locus has characteristics: an enhancer in the large intron separating the coding regions • They may be up to 1,000 base pairs away from the gene. Similar sequences that bind repressor proteins in eukaryotes are called silencers. There are fewer examples of these sequences known, and the mechanisms through which they act are not clear. Transcription _ Factors Transcription factors (and the genes that code for them) are called "trans" regulators. Trans Increased Rate regulatory proteins can diffuse of Transcription through the cell to their point of action. I 72 meulca • Genetic Regulation Transcription Factors The activator proteins that bind response elements are often referred to as transcription fac- tors. Specific Transcription Factors Specific transcription factors bind to enhancer regions or, in a few cases, to silencers and modu- late the formation of the initiation complex, thus regulating the rate of initiation of transcrip- tion. Each gene contains a variety of enhancer or silencer sequences in its regulatory region. The exact combination of specific transcription factors available (and active) in a particular cell at a particular time determines which genes will be transcribed at what rates.
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