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By P. Arakos. DeSales University. 2018.

This remarkable structure delivers ment called an electrocardiograph records these nutrients and oxygen from the mother to the fetus electrical impulses purchase 75 mg effexor xr with visa, using a needle 75 mg effexor xr with visa, or stylus generic effexor xr 37.5 mg line, that and removes waste products from the fetus and records the activity on graph paper. The pla- deflection of the electrocardiograph produces centa develops during pregnancy and is expelled waves or peaks designated by the letters P, Q, R, S, after the delivery of the infant. From the left atrium, blood heartbeat: the contraction phase (systole) when enters the (11) left ventricle and finally exits the the blood is forced out of the heart, and the heart through the aorta, where it travels to the relaxation phase (diastole) when the ventricles head and upper extremities. Systole produces the max- nonfunctional, most of the blood in the pulmonary imum force; diastole, the weakest. These meas- arteries is shunted through a connecting vessel urements are recorded as two figures separated called the (12) ductus arteriosus to the aorta. Systolic pressure is given first, Immediately after birth, the ductus arteriosus followed by diastolic pressure. As circulation increases in blood pressure of 120/80 mm Hg means a sys- the neonate, the increase of blood flow to the right tolic pressure of 120 with a diastolic pressure of atrium forces the foramen ovale to close. Connecting Body Systems-Cardiovascular System The main function of the cardiovascular system is to provide a network of vessels though which blood is pumped by the heart to all body cells. Specific functional relationships between the cardio- vascular system and other body systems are discussed below. Blood, lymph, and immune Endocrine • Cardiovascular system transports the • Cardiovascular system delivers oxygen and products of the immune system. Anatomy and Physiology 193 Connecting Body Systems-Cardiovascular System—cont’d • Cardiovascular system provides the ves- Musculoskeletal sels of the placenta during pregnancy for • Cardiovascular system removes heat and the exchange of nutrients and waste waste products generated by muscle con- products. Integumentary • Cardiovascular system provides blood Respiratory vessels in the skin to regulate body tem- • Cardiovascular system transports oxygen perature and carbon dioxide between lungs and • Cardiovascular system transports clotting tissues factors to the skin to control bleeding. It is time to review cardiovascular structures by completing Learning Activity 8–1. Medical Word Elements This section introduces combining forms, suffixes, and prefixes related to the cardiovascular system. Most emboli are blood clots (thrombi) that have been transported from a distant vessel by the blood. Other common causes include smoking, diabetes, high blood pressure, obesity, and familial tendency. Pathology Arteriosclerosis Many cardiac disorders, especially coronary artery Arteriosclerosis is a hardening of arterial walls disease, and valvular disorders are associated with that causes them to become thickened and brit- a genetic predisposition. This hardening results from a build-up of a ry as well as a physical examination is essential in plaquelike substance composed of cholesterol, the diagnosis of cardiovascular disease. Over time, some of the most serious cardiovascular diseases it builds up on the inside lining (tunica intima) have few signs and symptoms, when they occur of the arterial walls. Eventually, the plaque hard- they may include chest pain (angina), palpita- ens (atherosclerosis), causing the vessel to lose tions, breathing difficulties (dyspnea), cardiac elasticity. The location, duration, pattern of becomes difficult for blood to pass through the radiation, and severity of pain are important qual- blocked areas. Tissues distal to the occlusion ities indifferentiating the various forms of cardio- become ischemic. In many instances, blood hem- vascular disease and are sometimes characteristic orrhages into the plaque and forms a clot of specific disorders. When a throm- nature of the signs and symptoms of cardiovascu- bus travels though the vascular system it is called lar disorders, invasive and noninvasive tests an embolus (plural, emboli). Emboli in venous cir- are usually required to confirm or rule out a sus- culation may cause death. Sometimes cardiovascular disorders, the medical services of a plaque weakens the vessel wall to such an extent specialist may be warranted. Cardiology is the that it forms a bulge (aneurysm) that may medical specialty concerned with disorders of the rupture. The physician who treats Arteriosclerosis usually affects large- or medium- these disorders is called a cardiologist. One of the monly use endarterectomy to treat carotid artery major risk factors for developing arteriosclerosis is disease, peripheral arterial disease, and diseases of an elevated cholesterol level (hypercholesterolemia). Other major risk factors include age, family history, smoking, hypertension, and diabetes. Coronary Artery Disease Treatment for arthrosclerosis varies depending on the location and symptoms. In one method, In order for the heart to function effectively, it occluding material and plaque are removed from must receive an uninterrupted supply of blood. Plaque reduces Blood flow blood flow is blocked Area of Area of ischemia infarct Figure 8-8. Its major cause is the accumulation of it releases several highly specific cardiac enzymes, plaque which causes the walls of the artery to including troponin T, troponin I, and creatinine kin- harden (arteriosclerosis). Arrhythmia with an small incision in the skin and into the diseased abnormally rapid heart rate (tachycardia) or an blood vessel. Sometimes, the physician will place a hol- low, thin mesh tube (stent) on the balloon and position it against the artery wall.

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Ultrasound is obtained to evaluate mammographic masses to distinguish solid masses from fluid-filled cysts discount effexor xr 150 mg mastercard. The report classi- fies the mammogram and provides clear recommendations to treating physicians (Table 19 buy 37.5 mg effexor xr mastercard. Spiculated masses generic effexor xr 150mg visa, solid masses, and inde- terminate microcalcifications on mammography should be consid- ered suspicious and almost always require biopsy. This is the earliest form of breast cancer and is about 98% to 99% curable with appropriate treat- ment. Because the abnormality cannot be felt, an image must be used to guide the biopsy. Recently, stereotactic biopsy with a large-bore core needle or a vacuum-assisted device (Mammotome) has demonstrated accuracy equivalent to open biopsy in most patients. If a patient desires mastectomy or there are contraindica- tions to breast conservation, simple mastectomy (without axillary node dissection) may be performed. Several prospective trials clearly show a benefit to the addition of radiation therapy and systemic tamoxifen to lumpectomy. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from the National Surgi- cal Adjuvant Breast and Bowel Project B-17. Several classification systems are available to select patients who might safely skip radiation, most notably the Van Nuys Prognostic Index. Regular follow-up with mam- mography every 6 to 12 months is essential for this patient. Papilloma versus Malignancy (Case 6) The patient in Case 6 with the bloody nipple discharge might have breast cancer, although benign illnesses also can cause bloody dis- charge. The evaluation of women who present with nipple discharge is determined by the nature of the discharge. A milky discharge can be physiologic, secondary to numerous medications that affect pro- lactin, or due to pathologic conditions such as a pituitary tumor or ectopic prolactin production. A “fibrocystic discharge” is often brown, green, or black and usually is associated with duct ectasia or fibrocystic breasts. Clinical evaluation should be directed toward identifying palpable or mammographic lesions. Cytologic evaluation of nipple discharge has questionable usefulness, since decisions concerning surgery are made on clinical grounds. Likewise, galactography only occasionally is helpful, although some feel it helps guide excision. A negative galactogram should not be used as an excuse to avoid surgery when bloody dis- charge persists. Often, the discharge can be localized to one quadrant of the breast or even one duct, which is useful for guiding terminal duct excision. The bloody nature of the discharge, combined with its spontaneous expres- sion on several occasions, raises the level of suspicion of malignancy. The most common reason for bloody discharge is the presence of a papilloma, accounting for most cases. Terminal duct excision can be performed on an outpatient basis using local anesthesia with sedation. A circum- areolar incision may be used, and there usually is no need to close the resultant breast cavity. Younger patients who still expect to have chil- dren should be warned that interference with successful lactation might result. She does not have breast cancer and does not need specific treatment for her atypical hyperplasia. She has an increased risk of developing breast cancer based on her pathology findings. Her risk of developing breast cancer is approximately 5% over the next 5 years, with a lifetime risk of about 30%. Atypical ductal hyperplasia repre- sents a condition along the spectrum of breast cancer development. It is usually an incidental finding at the time of biopsy for a palpable or mammographic abnormality. Current consensus recom- mendations for this patient would suggest that she be examined twice a year at a specialized breast center. The tamoxifen group had nearly a 50% reduction in the incidence of new breast cancers.

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A computer-based intervention for improving the appropriateness of antiepileptic drug level monitoring order effexor xr 37.5 mg without prescription. Effectiveness evaluation of bar code implementation in hospital -- an illustration of out-patient pharmacy information system order effexor xr 75 mg on-line. Outcome-oriented quality assurance program for the clinical pharmacokinetics monitoring service generic 150mg effexor xr. Help to therapeutics by a daily computer monitoring of potential drug interactions. Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms. Optimisation of treatment by applying programmable rate-controlled drug delivery technology. Successful implementation of a comprehensive computer-based patient record system in Kaiser Permanente Northwest: strategy and experience. Implementation of online drug use criteria to facilitate nonformulary drug requests. Survey of patient and physician assessment of a compliance reminder device in the treatment of hypertension. Non-intrusive guideline-based electronic disease management programme: Principles and evaluation of a pilot. An efficient fault-tolerant order entry management information system based on special distributed client/server architecture. An efficient fault-tolerant out-patient order entry system based on special distributed client/server architecture. An empirical study of a computerized management system in ambulatory services at Chang Gung Memorial Hospital in Taiwan. Managing information technology: an empirical study of a computerized management system in ambulatory services at Chang Gung Memorial Hospital in Taiwan. Toward efficient medication error reduction: error-reducing information management systems. Medication reconciliation using natural language processing and controlled terminologies. The Belgian improvement study on oral anticoagulation therapy: A randomized clinical trial. Estimating the cost-effectiveness of quality- improving interventions in oral anticoagulation management within general practice. Predicting the impact of an electronic health record on practice patterns using computational modeling and simulation. Combined task delegation, computerized decision support, and feedback improve cardiovascular risk for type 2 diabetic patients. What nurses can do right now to reduce medication errors in the neonatal intensive care unit. Impact of implementation a unit-dose system and computer-assisted prescribing on medication errors. Treatment of hypertension by computer and physician - A prospective controlled study. Leapfrog: New initiative to help employee benefit plans adopt patient safety standards. Quantifying the impact of a clinical pharmacy program to support investments in automation technology. Hospital pharmacy staff attitudes towards automated dispensing before and after implementation. Translation and interpretation: the hidden processes and problems revealed by computerized physician order entry systems. Quantification and evaluation of pharmacist computer medication order entry errors. Personalized versus non-personalized computerized decision support system to increase therapeutic quality control of oral anticoagulant therapy: an alternating time series analysis. Development and pilot testing of computerized order entry algorithms for geriatric problems in nursing homes. Microcomputer-controlled administration of vasodilators following cardiac surgery: Technical considerations. Case study of the effects of office-based generic drug sampling on antibiotic drug costs and first-line antibiotic prescribing ratios. Interventions to reduce dosing errors in children: a systematic review of the literature.

Promoting Adequate Nutrition Head injury results in metabolic changes that increase calorie consumption and nitrogen excretion generic effexor xr 150 mg online. Early initiation of nutritional therapy has been shown to improve outcomes in patients with head injury effexor xr 75mg. Parenteral nutrition via a central line or enteral feedings administered via a nasogastric or nasojejunal feeding tube should be started within 48 hours after admission (Bader purchase 37.5 mg effexor xr, Littlejohns & March, 2003). Laboratory values should be monitored closely in patients receiving parenteral nutrition. Elevating the head of the bed and aspirating the enteral tube for evidence of residual feeding before administering additional feedings can help prevent distention, regurgitation, and aspiration. Enteral or parenteral feedings are usually continued until the swallowing reflex returns and the patient can meet caloric requirements orally. The patient emerging from a coma may become increasingly agitated toward the end of the day. It may indicate injury to the brain but may also be a sign that the patient is regaining consciousness. Strategies to prevent injury include the following: The patient is assessed to ensure that oxygenation is adequate and the bladder is not distended. Because prolonged use of an indwelling catheter inevitably produces infection, the patient may be placed on an intermittent catheterization schedule. Maintaining Body Temperature An increase in body temperature in the patient with a head injury can be the result of damage to the hypothalamus, cerebral irritation from hemorrhage, or infection. If the temperature increases, efforts are made to identify the cause and to control it using acetaminophen and cooling blankets to maintain normothermia (Bader & Littlejohns, 2004; Diringer, 2004). If infection is suspected, potential sites of infection are cultured and antibiotics are prescribed and administered. Use of mild hypothermia to 34° to 35° C (94° to 96° F) has been tested in small randomized controlled trials for at least 12 hours versus normothermia (control) in patients with closed head injury (Alderson, Gadkary & Signorini, 2005). The clinical trials with small samples showed improvement in patient outcomes but need to be repeated in larger trials. Because hypothermia increases the risk of pneumonia and has other side effects, this treatment is not currently recommended outside of controlled clinical trials. Maintaining Skin Integrity Patients with traumatic head injury often require assistance in turning and positioning because of immobility or unconsciousness. Prolonged pressure on the tissues decreases 412 circulation and leads to tissue necrosis. Potential areas of breakdown need to be identified early to avoid the development of pressure ulcers. Specific nursing measures include the following: Assessing all body surfaces and documenting skin integrity every 8 hours Turning and repositioning the patient every 2 hours Providing skin care every 4 hours Assisting the patient to get out of bed to a chair three times a day Improving Cognitive Functioning Although many patients with head injury survive because of resuscitative and supportive technology, they frequently have significant cognitive sequelae that may not be detected during the acute phase of injury. Cognitive impairment includes memory deficits, decreased ability to focus and sustain attention to a task (distractibility), reduced ability to process information, and slowness in thinking, perceiving, communicating, reading, and writing. Psychiatric, emotional, and relationship problems develop in many patients after head injury (Hsueh-Fen & Stuifbergen, 2004). Resulting psychosocial, behavioral, emotional, and cognitive impairments are devastating to the family as well as to the patient. A neuropsychologist (specialist in evaluating and treating cognitive problems) plans a program and initiates therapy or counseling to help the patient reach maximal potential (Eslinger, 2002). Cognitive rehabilitation activities help the patient to devise new problem-solving strategies. The retraining is carried out over an extended period and may include the use of sensory stimulation and reinforcement, behavior modification, reality orientation, computer-training programs, and video games. Even if intellectual ability does not improve, social and behavioral abilities may. The patient recovering from a traumatic brain injury may experience fluctuations in the level of cognitive function, with orientation, attention, and memory frequently affected. Many types of sensory stimulation programs have been tried, and research on these programs is ongoing (Davis & Gimeniz, 2004). When pushed to a level greater than the impaired cortical functioning allows, the patient may show symptoms of fatigue, anger, and stress (headache, dizziness). The Rancho Los Amigos Level of Cognitive Function is a scale frequently used to assess cognitive function and evaluate ongoing recovery from head injury. Progress through the levels of cognitive function can vary widely for individual patients. To allow the patient longer times of uninterrupted sleep and rest, the nurse can group nursing care activities so that the patient is disturbed less frequently. Back rubs and other measures to increase comfort can assist in promoting sleep and rest. Supporting Family Coping Having a loved one sustain a serious head injury can produce a great deal of prolonged stress in the family. Such changes are associated with disruption in family cohesion, loss of leisure pursuits, and loss of work capacity, as well as social isolation of the caretaker. The family may experience marital disruptions, anger, grief, guilt, and denial in recurring cycles (Hsueh-Fen & Stuifbergen, 2004).

In one approach insulin was chemically modified to introduce glucose order 150 mg effexor xr with mastercard, which has a specific binding site for the Con A lectin discount effexor xr 37.5 mg mastercard. The glycosylated insulin-Con A system exploits complementary and competitive binding behavior of Con A with glucose and glycosylated insulin 75 mg effexor xr fast delivery. The free glucose molecules complete with glucose-insulin conjugates bound to Con A, and thus, the glycosylated insulin is desorbed from the Con A in the presence of free glucose (Figure 16. As the pH decreases as a result of gluconic acid formation, the carboxylate groups are protonated and the electrostatic repulsion is reduced. This in turn causes shrinkage of the polymer chains to open pores for insulin release conjugates are released to the surrounding tissue and the studies have shown that the glucose-insulin conjugates are bioactive. In another approach, insulin was modified to introduce hydroxyl groups so that the hydroxylated insulin can be immobilized by forming a complex with phenylboronic acid groups on the support (Fig. The support can be hydrogel beads made of polymers containing phenylboronic acid, e. The hydroxylated insulin can be displaced by the added glucose and the displaced insulin can be released. While the approaches taken in the immobilized insulin systems are highly elegant, there is an inherent drawback of this approach. The approach requires modification of insulin to create a new chemical entity which would require full regulatory approval. The Massachusetts Institute of Technology has recently developed a 17 mm by 17 mm by 310 μm device containing 34 reservoirs. Controlled release from the device involves no moving parts with release from the individual reservoirs being initiated by applying an electric potential between the anode membrane and a cathode. The anode membrane undergoes electrochemical dissolution causing the release of solid, liquid or gel from the reservoir. The proof-of-principle release studies have demonstrated the controlled, pulsatile release of chemical substances from the device. Future integration of this technology with microchip-based bioanalytical technologies should facilitate the development of microchips in which a microbiosensor controls the release of drug in response to a biological stimulus, allowing both controlled pulsatile release and bioresponsive drug release from the same device. It is anticipated that the disease could be treated by introducing the enzyme-coding gene into bone marrow progenitors. Recent advance in genetic engineering technology has made it possible to regulate gene expression including transcription and translation in a variety of cell types. Such success has led to development of a second-type gene therapy making use of “surrogate” cells. Genetic modification of heterologous cells, rather than impaired cells, by viral or nonviral vectors endows the surrogate cells with a missionary function to provide the body with necessary proteins. Examples of the cells that are used include fibroblasts, endothelial cells, lymphocytes, keratinocytes, glial cells and mammary cells. These genetically modified cells may be housed in a polymeric implantable device for implantation into the patient. However, to make such a therapy reality, concerns over cell viability inside the implantable device have to be adequately addressed. The implant’s polymer composition and morphology would have to be optimized in order to maximize the life-span of the cells and to minimize host immune responses. The vascularization of the implant would be another determinant that plays an important role regarding cell viability because it enables the implant to receive nutrients necessary for their survival, to eliminate metabolic by-products and to provide the systemic entrance of therapeutic proteins. The disulfide bond is cleaved by electrons resulting from glucose transformation to gluconic acid by glucose oxidase. As drug delivery and targeting technologies advance, the requirements for the next generation of advanced drug delivery systems grows increasingly more demanding, forcing the development of more sophisticated systems. Previous technologies of sustained or zero-order release alone are not adequate to treat diseases requiring long-term care. Effective bioresponsive, modulated advanced drug delivery systems are now the “Holy Grail” of workers in this field. Fortunately the recent advancement of chemistry and biology provides the pharmaceutical scientist with the tools to develop more effective drug delivery systems which target the site-of-action of the drug and address the challenges of chronopharmacology. The future of drug delivery and targeting will rely on the integration of these disciplines and a wider appreciation of the need to address the challenges of drug delivery and targeting at an earlier stage in the drug discovery process. As a consequence, advanced drug delivery research will require a new generation of multidisciplinary pharmaceutical scientists to address these challenges in this new millennium. Explain the potential uses of (i) temperature-sensitive and (ii) pH-sensitive hydrogels in advanced drug delivery. Give examples of credible matrix systems which may have application in the bioresponsive delivery of insulin.

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However purchase effexor xr 75 mg on-line, even if these technologies are effective effexor xr 150 mg sale, they are expensive to implement and maintain and thus a review of the economic literature to determine cost-effectiveness and value for money for such interventions is warranted order effexor xr 150mg with amex. All studies passing the inclusion criteria that were considered to be cost or economics studies were reviewed and categorized into two groups based on the type of economic evaluation used in the analysis: (1) full economic evaluations; and (2) partial economic evaluations. A full economic evaluation is the comparative analysis of alternative courses of action in terms of both costs and consequences. Therefore, the economic evaluations which identify, measure, value, and compare the costs and consequences of the alternative being considered were further classified into one of the three categories: (1) cost-effectiveness analysis; (2) cost-utility analysis; 679 and 3) cost-benefit analysis. The label, partial economic evaluation, indicates that the studies do not entirely fulfill both of the necessary conditions for a full economic evaluation (i. However, cost analyses can provide useful information on ‘upfront’ costs 679 compared with ‘downstream’ cost avoidance. For this reason, both full economic evaluations and cost analyses were included in this review. In each of these classifications, articles were further categorized by setting (i. Descriptive information on the populations, interventions evaluated, the study year, perspective, and country of study were abstracted for each study. Data specific to the costs and effectiveness of each comparison were also abstracted and summarized in Appendix C, Evidence Tables 8a and 8b. The objective of the evaluation was to compare the costs and effects of a multifaceted intervention, including computerized reminders to physicians, aimed at improving prescribing of antihypertensive and cholesterol-lowering drugs compared with the passive dissemination of guidelines. The cost per additional patient started on a thiazide rather than another antihypertensive agent in the intervention group was compared with usual care. It was found that reduced drug expenditures based on increased use of thiazides did not outweigh the costs of the intervention. The authors commented that if the effect was sustained for a second year, the intervention would have been expected to lead to savings. Over the 1-year study period, the authors found that from a societal perspective, the intervention dominated standard care (i. From the health care payer perspective, the incremental cost-effectiveness ratio was €61 per percentage point reduction in the St. Using information obtained from a systematic review of the literature, 681 Karnon et al. It was noted that the monetary value of lost health needed to be included for the interventions to have a high probability of producing positive net benefits. Partial Economic Evaluations Most of the economic literature reported the results of partial evaluations (26 of 31 studies, 84 percent). In other words, the costs of the alternatives were examined separately and the effectiveness, efficacy, or both measures were not used in the analyses, which results in an inability to answer efficiency questions about an intervention. The study compared patients whose microbiologic data were processed in the normal manual manner in the pharmacy to patients whose microbiological data were processed using the computer software. The study patients were matched by diagnosis related groups to patients in the control group. Additionally, the control group patients were adjusted for severity to make the groups more comparable. Antimicrobial utilization was managed by an existing antimicrobial management team using the system in the intervention arm and without the system in the control arm. Direct antibiotic costs, as well as costs incurred by observed adverse events, were similar. A Canadian study in an orthopedic institution assessed the safety and potential cost savings of a computerized, laboratory-based program (i. It is important to note that the cost estimates and potential cost savings are speculative and are meant to be illustrative and not conclusive in nature. A before-after study of the system found no significant difference in the total inpatient costs among the groups before and after intervention. The authors stated that it took over 5 years to realize a net benefit and over 7 years to realize an operating budget benefit. Based on total costs per admission, no significant difference was seen in any of the U. Based on the data from 6 months before and 6 months after the intervention, a 47 redistribution of workload was found. The authors claim that if these effects were extrapolated to all medicine service admissions at that hospital, the projected savings in charges per year would be $3 million in 1993 U. In both studies, care recommendations were displayed electronically to either physicians, pharmacists, or both physicians and pharmacists, compared with no care recommendations. In the asthma and chronic obstructive lung disease study, the authors found no difference in total costs (i. It was noted that these savings coincided with only modest quality improvements in projected mortality rates and length of stay. The impact on total costs was markedly different in the two groups: €264,658 in the usual care group and €170,061 in the intervention group. When compared with a 6-month period where cost information was not displayed, it was concluded that no impact was found on overall drug costs to patients that could be related to the intervention.

The mechanism of resis- tance toward trimethoprim described here illustrates the power of the selection pressure exerted by the wide and ubiquitous spread of antibiotics: a power that can force resistance genes to travel horizontally into the pathogens of those infections we try to treat purchase 75mg effexor xr. The horizontal resistance gene transport is effected by genetic transport mechanisms such as plasmids purchase effexor xr 150 mg free shipping, transposons order 75 mg effexor xr, and integrons (see Chapter 10), earlier evolved, probably for adaptation to changes in the environment, and now, in turn, used for adaption to the dramatic environmental changes that our use of antibiotics has led to. There is a hint of the origin of the resistance gene dfr9 in the upper part of the phylogenetic tree. As mentioned, this gene was found on large transferable plasmids in isolates of E. A closer study of the gene environment on the plasmid showed it to be inserted in a crippled transposon, which could be identified as Tn5393, which was crippled because only the right-hand part could be found in the plasmids (Fig. The transposon Tn5393 was originally found and character- ized from a plasmid in the plant pathogen Erwinia amylovora, causing fire blight in apple trees. This pathogen caused large losses to fruit farmers, who tried to protect their crops by spraying their apple trees with a solution of streptomycin. The pathogen soon became resistant, however, by taking up two streptomycin resistance genes, strAandstrB (mediating phosphorylation of streptomycin, see Chapter 6). A closer characterization of the resistance showed the two genes to be inserted in a transpo- son termed Tn5393, which in turn was borne on a plasmid in E. The lower part of the figure shows the insertion of dfr9instrAof the right end of Tn5393 as found on a plasmid in an isolate of Ecolifrom swine (see the text). That is, a genetic element from a plant pathogen is shown to carry trimethoprim resistance in a gut isolate from swine on another continent. Modern swine rearing includes herds of hundreds of animals which share gut bacteria. This, in turn, means the existence of enormous populations of geneti- cally communicating bacteria, from which also very rare genetic events can be selected. In this case a gene for trimethoprim resistance borne on a rare movable genetic element could have surfaced under the selection pressure of trimethoprim, which has frequently been used for the treatment of swine diarrhoeas. This might also be an example of how antibiotic resistance genes are brought forward in farm animals, later to find their way into human pathogens. All these examples show bacterial adaptation to the envi- ronmental change induced by the ubiquitous use of trimetho- prim and by acquiring a large number of different resistance genes, probably originating in a large variation of other organ- isms. There is a corresponding mechanism of resistance against trimethoprim in staphylococci. This is effected by the transposon- borne and trimethoprim-resistant dihydrofolate reductase S1. The resistance enzyme is almost identical to the chromosomal dihydrofolate reductase of S. Another plasmid-borne resistance enzyme, S2, mediating trimethoprim resistance horizontally, was observed in S. The mecha- nisms of horizontal uptake of these genes in Campylobacter could be surmised, since they were found inserted in those genetic elements they were earlier found to be used for transfer. Regarding dfr9, remnants of its earlier Tn5393 surroundings were observed around it. The interpretation of these findings seems to lead to a contradiction, since the trimethoprim resistance genes acquired do not offer any advantage for survival in the presence of trimethoprim. As mentioned earlier, Campylobacter bacteria lack a gene for dihydrofolate reductase and are thus innately resistant to trimethoprim. Could it be that the lack of a chromosomal gene for dihydrofolate reductase represents an evolutionarily older and less efficient metabolic pattern? The trimethoprim resistance dihydrofolate reductases mobilized by our use of trimethoprim and acquired by Campy- lobacter could possibly enhance the viability of these bacteria, and with that, their pathogenity. It ought to be added that either dfr1ordfr9 or both presently seem to occur in most or all clinical isolates of C. Experimental Test of the Reversibility of Trimethoprim Resistance In the laboratory experiment of isolating spontaneous sulfonamide-resistant mutants of E. This trade-off between resistance and fitness seems to be a logical outcome when a bacterium adapts its evolutionary optimized genotype to one acutely needed in the presence of an antibiotic. The very important question of possible reversion of resistance should antibiotic use be discontinued or reduced was tested experimentally in a large clinical experiment in a county (Kronoberg) in Sweden. The health care system is funded at the county level and includes two hospitals and 25 primary health care centers. All 464 physicians in the area were asked to substitute trimethoprim-containing medicines with other antibacterials in the treatment of urinary tract infections. A prompt and sustained decrease of 85% in the total trimethoprim prescription was reached rapidly, as judged from the sales figures of the distributor.

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