By R. Sigmor. College of Eastern Utah. 2018.
The healer has a feel for each individual patient and the treatment is modified according to the needs and personality of the patient generic 25mg viagra with visa. Start of hospitals and universities Sixteenth to Important discoveries in anatomy and physiology but no pharmacological eighteenth advances in middle ages order 25mg viagra amex. Patient care was personalized for lack of centuries standard treatments 1789 Founding of homeopathy based on “like cures like” by Samuel Hahnemann in Germany viagra 100mg line. Homoeopathic prescribing is highly individualized to a person’s “constitutional picture” rather than to specific diseases Nineteenth Start of modern medicine discount 50 mg viagra with mastercard. Claude Bernard’s (1813–1878) introduction of century, late the scientific method into medicine, founded on observation and proved by experiments, started to endanger personal aspects of treatment Twentieth century Most of the advances in medicine were made in this century including imaging techniques, laboratory diagnostics and modern surgical techniques. Start of impact of molecular biology on pharmacology 1985 Discovery of polymerase chain reaction (Mullis et al. Cell and gene therapies 1993 Concept of using molecular nanotechnology to base medical therapy on the biochemical individuality of specific patients (Fahy 1993) 1995 Coining of the term “proteomics” (Wilkins et al. Modern medicine is considered to start in the nineteenth century although several important discoveries, notably smallpox vaccine were made close to the end of the eighteenth century. Modern pharmaceuticals and drug discovery started to develop in the twentieth century with most of the advances taking place in the second half and the most important ones in the last decade. The role of physicians in making necessary judgments about the medicines that they prescribe has often been referred to as an art, reflecting the lack of objective data available to make decisions that are tailored to individual patients. Now we are on the verge of being able to identify inherited differences between individuals, which can predict each patient’s response to a medicine. Review of history of medicine shows that development of personalized medicine will be an evolution and not revolution in medicine. Medicine has always been evolving and will continue to evolve although the progress may appear slow at times. Universal Free E-Book Store 6 1 Basic Aspects Molecular Biological Basis of Personalized Medicine Although several factors are involved in the development of personalized medicine, developments in molecular biology have played an important role. The human genome is extremely complex, and the estimated number of genes has varied considerably during the past years. The investiga- tors described a set of 2,001 potential non-coding genes based on features such as weak conservation, a lack of protein features, or ambiguous annotations from major databases. Most of these genes behave like non-coding genes rather than protein-coding genes and are unlikely to code for proteins under normal circumstances. If one excludes them from the human protein-coding gene catalog, the total number of genes in the human genome is reduced to ~19,000. The federal project involved 440 scientists from 32 laboratories around the world. Nine years after launch, its main efforts culminate in the publication of 30 coordinated papers (Skipper et al. Collectively, the papers describe 1,640 data sets generated across 147 differ- ent cell types. Among the many important results there is one that stands out above them all: more than 80 % of the human genome’s components have now been assigned at least one biochemical function. The system of switches select the genes used in a cell as well as determine when they are used and their fate, e. Many complex diseases appear to be caused by tiny changes in hundreds of gene switches. In the case of identical twins, small changes in environmen- tal exposure can slightly alter gene switches, with the result that one twin gets a disease and the other does not. Gene switches are linked to a range of human diseases: multiple sclerosis, lupus, rheumatoid arthritis, Crohn’s disease, celiac disease and even to traits like height. The discoveries also reveal the genetic changes that are important in cancer and why.
Once the molecule is Universal Free E-Book Store Role of Life Sciences Industries 599 labeled purchase 100 mg viagra overnight delivery, it is injected into the patient viagra 50 mg without a prescription. The positrons that are emitted from the isotopes then interact locally with negatively charged electrons and emit what is called anni- hilating radiation cheap 100 mg viagra otc. It is the timing and position of the detection that indicates the position of the molecule in time and space discount 100mg viagra mastercard. Images can then be constructed tomographically, and regional time activities can be derived. The kinetic data produced provide information about the biological activity of the molecule. Molecular imaging provides in vivo information in contrast to the in vitro diagnostics. Moreover, it provides a direct method for the study of the effect of a drug in the human body. Personalized medicine will involve the integration of in vitro genotyping and in vivo phenotyping techniques. These modalities along with ultrasound and optical imaging (bioluminescence, fluorescence, near- infrared imaging, multispectral imaging) have become used increasingly in pre- clinical studies in animal models to document the effects of genetic alterations on cancer progression or metastases, the detection of minimal residual disease, and response to various therapeutics including radiation, chemotherapy, or biologic agents. The field of molecular imaging offers potential to deliver a variety of probes that can image noninvasively drug targets, drug distribution, cancer gene expres- sion, cell surface receptor or oncoprotein levels, and biomarker predictors of prog- nosis, therapeutic response, or failure. Some applications are best suited to accelerate preclinical anticancer drug development, whereas other technologies may be directly transferable to the clinic. Efforts are underway to apply noninvasive in vivo imaging to specific preclinical or clinical problems to accelerate progress in the field. By enabling better patient selection and treatment monitoring strategies, molecular imaging will likely reduce the future cost of drug development. As anticancer strategies become more directed towards a defined molecular tar- get, we need information that is relevant to humans about whether the molecular target is expressed, the selectivity and binding of the compound for that target, and the effects of such an interaction. The following is an example of the use of molecu- lar imaging in drug discovery for cancer. The use of noninvasive bioluminescence imaging has been demonstrated in a high-throughput cell-based screen of small molecules that activate p53 responses and cell death in human tumor cells carrying a mutant p53 Universal Free E-Book Store 600 20 Development of Personalized Medicine (Wang et al. Some compounds do not induce significant p73 expression but induce a high p53-responsive transcriptional activity in the absence of p53. The results establish the feasibility of a cell-based drug screening strategy targeting the p53 transcription factor family of importance in human cancer and provide lead compounds for further development in cancer therapy. These findings emphasize the growing role of imaging technology in aiding researchers in the development of personalized cancer treatments. The therapeutic effects of the small molecule com- pounds will be explored in different types of cancer and the potential toxicities of these compounds will be evaluated. Further efforts are needed in this area and pharmaceutical industry need to get involved besides the academic investigators and the companies providing the equip- ment and other materials. The major challenge for drug development is to overcome the lack of specific tracers and ligands available for in vivo imaging. Here, the problem is often not one of specificity for the molecular interaction or pathway, but rather of background owing to non-specific binding in vivo, peripheral metabolism and/or poor penetration across endothelial barriers. In vivo assays of molecular interactions and pathways should be sufficiently cancer-specific to be of use as ther- apeutic targets. Such probes could provide therapeutically relevant functional mea- sures of disease status and, hence, assays of potential responsiveness. Systems already in place for cancer include the imaging of proliferation and its relevance to anti-proliferative agents, blood flow and its relevance to antiangiogenic agents, and gene expression with relevance to gene therapy. If an in vivo diagnostic is available to monitor the effects of numerous available antiangiogenesis agents on tumors, it can help us to define responder and non-responders. The joint goal is to develop a cost-effective, readily accessible molecular imaging technology that can help more clinics and hospitals accurately diagnose cancer and pre-screen patients for therapy. There is a good correlation between the degree of uptake of Hynic-Annexin V measured on images of head and neck tumors and the degree of cell death in the tumors demonstrated on microscopic examina- tion following surgical removal of the tumors.
Ultrasonography of the suprahyoid Introduction/Background: In the rehabilitation of stroke patients purchase 100mg viagra mastercard, muscles has the possibility of becoming useful method for clinical while the amelioration of the paretic side is important discount 100 mg viagra fast delivery, strengthening application through repeated practice discount 50mg viagra visa. Introduction/Background: To investigate assisted balloon dilata- tion with surface anesthesia to treat nasopharyngeal carcinoma 805 after radiotherapy which leads to benign stricture of cricopharyn- geus and dysphagia buy viagra 50mg on-line. Gonzalez-Suarez1 treated with low frequency electric stimulation and assisted bal- 1University of Santo Tomas Hospital, Physical Medicine and Reha- loon dilatation for 3 weeks. All of them were assessed by vide- bilitation, Manila, Philippines ofuoroscopic swallowing study and conscious of diffculty swal- lowing pre and post treatment. Results: Pharyngeal delay time Introduction/Background: In the literature, there is no clear con- and cricopharyngeal opening of both groups were improved after sensus regarding terminology and etiology for pain in the anterior treatment (p<0. However, based on the invalid swallowing as well as the aspiration rate were decreased present literature, it may not be possible to decide what is the most (p<0. Among them there was a sig- We have selected the case of an athlete who underwent a new tech- nifcant decrease (p<0. Conclusion: of the patient and physicians (orthopedic surgeon, anesthesiolo- Balloon dilatation combined with low frequency electric stimu- gist, and sonologist) present during the procedure was conducted lation therapy will have synergistic effect and they can improve to validate and supplement the information obtained from the chart patients’ swallowing function after radiation induced cranial review. Pain scores were graded retrospectively by recall of pre- nerve damage, thus improve the survival quality of patients. Results: This study assisted balloon dilatation without anesthesia had better effect described an ultrasound-guided, percutaneous technique that uti- than that of surface anesthesia. Stewart2 Mackay Memorial Hospital, Physical Medicine and Rehabilita- 1The Hong Kong Polytechnic University, Rehabilitation Sciences, tion, Taipei, Taiwan Kowloon, Hong Kong- China, 2Hong Kong Rugby Football Union, Introduction/Background: Sport for people with disabilities is an Hong Kong Rugby Football Union, Hong Kong, Hong Kong- China important measure for both rehabilitation and participation. However, their sport in- Introduction/Background: Rugby is a demanding game with many juries and musculoskeletal injuries are not understood. Material physical collisions and tackles potentially leading to musculoskel- and Methods: We set up a special clinic for disabled sports athletes etal injuries. Because of the nature of the sports, rugby not only in a tertiary hospital in Taipei Taiwan. This clinic was run on one requires a range of individual skills but also well-developed ftness. This clinic is organ- The role of physical ftness in the risk of rugby-related injury is ized by a rehabilitation specialist with international classifcation not well known. The purpose of this prospective cohort study was experience, one resident, one nurse, and equipped with radiogra- to determine the infuence of physical ftness as risk factors for in- phy, musculoskeletal ultrasonography and other imaging modali- juries, taking exposure time into account. Results: Thirteen national and international level Rugby players from 3 Hong Kong universities (n=84; 75M:9F; athletes were evaluated. Players were asked to complete a questionnaire relating to letes, 3 specialize in para-badminton, 1 in wheelchair dance, 1 in demographic characteristics, playing experience and history of pre- archery and 1 in athletics. The players then underwent pre-season assessment spinal cord lesion, 1 with lower limb trauma and 1 with achondro- of physical ftness including power, strength, speed, agility, endur- plasia. Most patients reported more than 2 active musculoskeletal ance, stability and fexibility. Noteworthy was that many of them reported multiple during the season were reported online. At the end of the season, in- experiences of offce visits in clinics and treatment failures. Shoul- dependent variables were selected and analysed using Cox propor- der pain and elbow pain were top two complaints. Results: complaints were hand numbness, hip pain, upper back pain and low The injury incidence was 47. A majority of injuries (70%) occurred in the frst visiting the sport clinic for disabled athletes will help further im- 35 hours of exposure. The aim of this trail is sys- history and female players are at a greater risk for rugby-related tematically evaluate the protective effects of Baduanjin exercise injuries in university players. The transition from off-season train- on ischemic stroke risk in the community elder population with ing to increase in training volume may need careful consideration high risk factors. Acknowledgments: The authors thank the Hong participants were randomly allocated into the Baduanjin exercise Kong Rugby Football Union and players from the 3 university and control group (usual physical activity group) in a 1:1 ratio.
Antibiotic Kinetics in the Multiple-System Trauma Patient 527 b-lactam alternatives where toxicity concerns are minimized and larger doses can be safely utilized discount 75 mg viagra overnight delivery. The data that evaluate other antibiotics in preventive indications in trauma patients is very limited viagra 25mg with mastercard. They identified lower antibiotic concentrations in selected patients in the recovery room generic viagra 50mg without a prescription, and found that lower postoperative antibiotic concentrations were predictive of postoperative infections order 100 mg viagra with amex. They identified blood loss, extensive intraoperative resuscitation, and expanded Vd as likely causes for reduced postoperative antibiotic concentrations and recommended consideration for increased preop- erative dose of preventive antibiotics. They recommended re-dosing or continuous infusion as a requirement for effective use of preventive antibiotics in this population. Aminoglycosides The aminoglycosides more than any antibiotic group have been studied most extensively in the setting of critical illness. Nephro- and ototoxicity have been the driving issues that have stimulated pharmacokinetic studies of the aminoglycosides. However, the data indicate that perhaps more patients have been underdosed than have received toxic levels of these antibiotics. Given that gentamicin and the other aminoglycosides have been demonstrated to have highly variable pharmacokinetics even with patients that appear to have normal kidney function (6), it is not surprising that physiologic changes of trauma and clinical fever will further compound an already difficult situation. All study patients received at least one aminoglycoside with the majority receiving gentamicin or tobramycin. The Vd increased approximately 50% greater than normal for this population with one patient demonstrating a threefold increase. Using individual patient pharmacokinetic parameters, adjustments in gentamicin doses ranged from 1. In this latter study, drug elimination rates were strongly influenced by the patient’s serum creatinine as a marker of clinical renal function. Despite larger doses that were required, doses of the aminoglycosides were given less frequently with patients having a creatinine above 1 mg/dL. They identified 59% of patients that had blood concentration of the antibiotic that was significantly below expected concentrations. The expanded Vd was considered to be responsible for the low blood concentrations. Dasta and Armstrong (10) studied aminoglycoside pharmacokinetics in 181 critically ill patients in a surgical intensive care unit. Additional studies have validated that the observations of increased Vd and highly variable T1/2 are applicable to all of the aminoglycosides in trauma (11) and intensive care unit patients (12). Understanding these changes of aminoglycosides under circumstances of trauma, fever, and critical illness should lead to pharmacokinetic dosing and changes in the management of these patients. Once-daily dosing of aminoglycosides has become very common at present, but again the pharmacokinetic observations have demonstrated that conventional doses will be inadequate, especially for the younger trauma patient with normal renal function. Vancomycin Like the aminoglycosides, the pharmacokinetics of vancomycin is highly variable among patients with normal renal function (14). They assumed and documented that the Vd of vancomycin was essentially that of total body water, or 0. In selected cases, the Vd was so high that it actually exceed the theoretical maximum of 1. Pharmacokinetic dosing required a 20% increase in the predicted dose of vancomycin, but a 50% increase in the interval between doses reflected a longer T1/2 than expected. Vancomycin clearance was 143 mL/min in the burn patient which was more than twice as great as that seen in control patients (68 mL/min). Vancomycin patients required larger and more frequent doses of the drug to achieve satisfactory peaks and troughs during therapy. The hyperdynamic circulation of the burn patient with normal kidney function was thought to be the basis for accelerated drug clearance. Garrelts and Peterie (17) made similar observations with respect to a reduced T1/2 in burn patients receiving vancomycin. Van Dalen and Vree (18) studied Vd and T1/2 in critically ill patients after the administration of ceftriaxone, the most commonly employed third-generation cephalosporin.