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She also describes the loss of appetite over the last 12 hours safe 100 mg viagra soft, but denies nausea and vomiting. On pelvic examination you elicit cervical motion tenderness and note cervical exudates. On physical examination, the patient complains of pain when you flex his knee with internal rotation at his hip. Inspection reveals the tube is pulled out from the stoma, but is still in the cutaneous tissue. Insert a Foley catheter into the tract, instill water-soluble contrast, and obtain an abdominal radiograph prior to using for feeding. Discharge patient with antibiotics, pain medicine, and instructions to drink large amounts of water and cranberry juice. Physical examination reveals a tender (2 × 2)-cm bulge with erythema below the inguinal ligament and abdominal disten- sion. Over the next few hours, the patients begin to improve, the vomiting stops and their abdominal pain resolves. On examination, you note mild abdominal distention and diffuse abdominal tenderness without guarding. The pain is associated with nausea, vomiting, diarrhea, anorexia, and a fever of 100. Based on the principles of emergency medicine, what are the three priority considerations in the diagnosis of this patient? On physical examination you observe vaginal trauma and scattered bruising and abrasions. Which of the following medications should be offered to the patient in this scenario? Ceftriaxone, azithromycin, metronidazole, antiretrovirals, emergency contraception b. Ceftriaxone, azithromycin, tetanus, metronidazole, antiretrovirals, emergency contraception Abdominal and Pelvic Pain 101 116. His past medical history includes prostate cancer, left total hip replacement, appendectomy 25 years ago, right iliac artery aneurysm repair 5 years ago, incisional hernia repair 4 years ago, and irritable bowel syndrome. He recalls having similar pain 1 week ago that resolved sponta- neously after 10 minutes. He was recently well and reports no fever, diar- rhea, urinary frequency, or dysuria. Which of the following is an important predisposing factor for the devel- opment of the condition seen in this individual? Provide oxygen via face mask, give morphine sulfate, and order a transvaginal ultrasound. She tells you that she has had this similar presentation four times over the past 2 months. Which of the following extraintestinal manifestations is associated with Crohn disease but not ulcerative colitis? During this time, she has been to the clinic twice, with negative urine cul- tures each time. Her condition has not improved with antibiotic therapy with sulfonamides or quinolones. Which of the following organisms is most likely responsible for the patient’s symptoms? He also describes nausea and vomiting and states he usually drinks 6 pack of beer daily, but has not had a drink for 2 days. Examination shows voluntary guarding and tenderness to palpation of his epigastrium. Admit to the hospital for medical management and supportive care Abdominal and Pelvic Pain Answers 74. The typical patient with mesenteric ischemia may initially present with “pain that is out of proportion to the examination” (ie, although the patient is in pain, the abdomen is neither rigid, nor signif- icantly tender on physical examination). Abdominal distention and peri- toneal signs are late findings and signal the presence of bowel infarction. Although rare, the finding of gas in either the bowel wall (pneumatosis intestinalis) or in the portal venous system is strongly suggestive of intesti- nal infarct. Rotavirus, typ- ically a disease of young children and Norwalk virus are the most frequent etiologic agents. Though dehydration is a common complication, these illnesses are usually self-limited, requiring only supportive care. In the adult, the lower esophageal sphincter is the most common site for impactions. When impaction occurs, patients usually feel some discomfort, sometimes substernal chest pain, anxiety, and progressive dysphagia. Most of the time, 105 106 Emergency Medicine the patient can accurately locate the position of the impacted foreign body.

Building from Scratch: Atoms and Elements All matter — be it solid purchase viagra soft 100mg without a prescription, liquid, or gas — is composed of atoms. An atom is the smallest unit of matter capable of retaining the identity of an element during a chemical reaction. An element is a substance that can’t be broken down into simpler substances by normal chemical reactions. There are 92 naturally occurring atoms in nature and 17 (at last count) artificially created atoms for a total of 109 known atoms. However, additional spaces have yet to be filled in on the periodic chart of elements, which organizes all the elements by name, symbol, atomic weight, and atomic number. Atoms are made up of the subatomic particles protons and neutrons, which are in the atom’s nucleus, and clouds of electrons orbiting the nucleus. The atomic weight, or mass, of an atom is the total number of protons and neutrons in its nucleus. The atomic number of an atom is its number of protons or electrons; conveniently, atoms always have the same number of protons as electrons, which means that an atom is always electrically neutral because it Part I: Building Blocks of the Body 8 always has the same number of positive charges as negative charges. Opposite charges attract, so negatively charged electrons are attracted to positively charged protons. The more protons there are in the nucleus, the stronger the atom’s positive charge is and the more electrons it can attract. Electrons circle an atom’s nucleus at different energy levels, also known as orbits or shells (see Figure 1-1). Each orbit can accommodate only a limited number of electrons and lies at a fixed distance from the nucleus. Each level must be filled to capacity with electrons before a new level can get started. The orbit closest to the nucleus, which may be referred to as the first level or first shell, can accommodate up to two electrons. The second level can have eight electrons and the third also can have eight electrons. Higher orbits exist, but anatomy and physiology students only need to know about the first three levels. In other words, isotopes are alternate forms of the same chemical element, so they will always have the same number of pro- tons as that element, but a different number of neutrons. Ions: Because electrons are relatively far from the atomic nucleus, they are most susceptible to external fields. Getting an extra electron turns an atom into a negatively charged ion, or anion, whereas losing an electron creates a positively charged ion, or cation. To keep anions and cations straight, think like a compulsive dieter: Gaining is negative, and losing is positive. Acid: A substance that becomes ionized when placed in solution, producing + positively charged hydrogen ions, H. Bases are referred to as being more alka- line than acids and are known as proton acceptors. Chapter 1: The Chemistry of Life 9 Answer these practice questions about atoms and elements: 1. For an atom with an atomic number of 19 and an atomic weight of 39, the total number of neu- trons is a. Fill in the blanks to complete the following sentences: Different isotopes of the same element have the same number of 7. Part I: Building Blocks of the Body 10 Compounding Chemical Reactions Atoms tend to arrange themselves in the most stable patterns possible, which means that they have a tendency to complete or fill their outermost electron orbits. The force that holds atoms together in collections known as molecules is referred to as a chemical bond. There are two main types and some secondary types of chemical bonds: Ionic bond: This chemical bond (shown in Figure 1-2) involves a transfer of an elec- tron, so one atom gains an electron while one atom loses an electron. One of the resulting ions carries a negative charge, and the other ion carries a positive charge. Na Cl Na+ Cl– Figure 1-2: Sodium atom (Na) Chlorine atom (Cl) Sodium atom (Na) Chloride ion Ionic bonding. Sodium chloride (NaCl) Covalent bond: The most common bond in organic molecules, a covalent bond (shown in Figure 1-3) involves the sharing of electrons between two atoms. The pair of shared electrons forms a new orbit that extends around the nuclei of both atoms, producing a molecule. There are two secondary types of covalent bonds that are relevant to biology: H H H H C + H C H H H H H Carbon atom H Figure 1-3: H Covalent bonding. Hydrogen atoms Methane molecule • Polar bond: Two atoms connected by a covalent bond may exert different attractions for the electrons in the bond, producing an unevenly distrib- uted charge.

A priori nursing science: All research flows from a appreciation is the process of apprehending in- theoretical perspective buy cheap viagra soft 50mg on line. Every step of the inquiry, formation or manifestations of patterning including the type of questions asked, the con- emerging from the human/environmental field ceptualization of phenomena of concern, choice mutual process. The process of pattern knowing of research design, selection of participants, se- and appreciation is the same in the research en- lection of instruments, and interpretation of deavor as described earlier in the Rogerian prac- findings is guided by the science of unitary tice methodology. It is important to note that because of the aware of dynamic unpredictability and contin- incongruency between ontology and episte- uous change and is open to the idea that pat- mology of Rogerian science with assumptions terns in the inquiry process may change in the in quantitative designs, Carboni (1995b) ar- course of the study that may not have been en- gues that the researcher must select qualitative visioned in advance. It is essential that the researcher docu- ods with Rogerian science and argue that the ment and report any design changes. Pattern synthesis: Rogerian science emphasizes hence, both qualitative and quantitative meth- synthesis rather than analysis. The separation of parts is not consistent ence is reflected in the nature of questions with Rogers’ notion of integrality and irre- asked and their theoretical conceptualization ducible wholes. However, qualitative designs, the whole emerging from the human/environ- particularly those that have been derived from mental mutual field process. Synthesis allows the postulates and principles of the science for creating and viewing a coherent whole. Shared description and shared understanding: the natural settings where the phenomenon of Mutual process is enhanced by including par- inquiry occurs naturally, because the human ticipants in the process of inquiry where possi- field is inseparable and in mutual process with ble. Any “manipulation” of participants in the study enhances shared “variables” is inconsistent with mutual process, awareness, understanding, and knowing par- unpredictability, and irreducibility. The researcher and the researcher-into are inte- are the best judges of the authenticity and va- gral: The principle of integrality implies that lidity of their own experiences, perceptions, the researcher is inseparable and in mutual and expressions. Participatory action designs process with the environment and the partici- and focus groups conceptualized within pants in the study. Each evolves during the re- Rogerian science may be ways to enhance mu- search process. The researcher’s values are also tual exploration, discovery, and knowing par- inseparable from the inquiry. Evolutionary interpretation: The researcher in- and environmental field are integral to each terprets all the findings within the perspective other. Purposive sampling: The researcher uses pur- the findings are understood and presented posive sampling to select participants who within the context of Rogers’ postulates of en- manifest the phenomenon of interest. Recogni- ergy fields, pandimensionality, openness, pat- tion of the integrality of all that is tells us that tern, and the principles of integrality, reso- information about the whole is available in in- nancy, and helicy. There is be explored is participatory action and cooperative strong support for the appropriateness of phenom- inquiry (Reason, 1994), because of their congru- enological methods in Rogerian science. Reeder ence with Rogers’ notions of knowing participation (1986) provided a convincing argument demon- in change, continuous mutual process, and inte- strating the congruence between Husserlian phe- grality. Cowling (1998) proposed that a case- nomenology and the Rogerian science of unitary oriented approach is useful in Rogerian research, human beings: because case inquiry allows the researcher to attend to the whole and strives to comprehend his or her [G]iven the congruency between Husserlian phenom- enology and the Rogerian conceptual system, a essence. Husserlian flows from the postulates, principles, and concepts phenomenology as a rigorous science provides just relevant to the conceptual system. Creativity, mystical experiences, tran- the findings in a way that is consistent with Rogers’ scendence, sleeping-beyond-waking experiences, notions of unpredictability, integrality, and nonlin- time experience, and paranormal experiences as earity. Emerging interpretive evaluation methods, they relate to human health and well-being are also such as Guba and Lincoln’s (1989) Fourth of interest in this science. Feelings and experiences Generation Evaluation, offer an alternative means are a manifestation of human/environmental field for testing for differences in the change process patterning and are a manifestation of the whole within and/or between groups more consistent (Rogers, 1970); thus, feelings and experiences rele- with the Science of Unitary Human Beings. Discrete stages of theory development, designs that generate particularistic biophysical phenomena are usually descriptive and explanatory knowledge are relevant not an appropriate focus for inquiry because to the Science of Unitary Human Beings. New concepts with power have been found with anxiety, chronic that describe unitary phenomena may be devel- pain, personal distress, and hopelessness (Caroselli oped through research. For example, the metaphor (Butcher, 2002b), caring (Smith, 1999), and energy “I feel at one with the universe” reflects a high de- (Leddy, 2003; Todaro-Franceschi, 1999) are exam- gree of awareness of integrality; “I feel like a worn- ples of concepts that have been reconceptualizied in out shoe” reflects a more restricted perception of one’s potential (Johnston, 1994; Watson et al. Future research may focus on developing an Researchers need to ensure that concepts understanding of how human field image changes and measurement tools used in the inquiry in a variety of health-related situations or how are defined and conceptualized within a human field image changes in mutual process with unitary perspective. Diversity is inherent in the evolution of the a way congruent with Rogers’ principles and postu- human/environmental mutual field process. Researchers need to ensure that concepts and evolution of the human energy field is character- measurement tools used in the inquiry are defined ized by the creation of more diverse patterns re- and conceptualized within a unitary perspective. Two major concepts— lected patterning modalities designed to foster har- “my motor is running” and “my field expansion”— mony and well-being (Hastings-Tolsma, 1992; are rated using a semantic differential technique Watson et al. Examples of indicators of higher veloped within and unitary science perspective that human field motion include feeling imaginative, vi- may be used in a wide variety of research studies sionary, transcendent, strong, sharp, bright, and ac- and in combination with other Rogerian measure- tive. Indicators of relative low human field motion ments include: include feeling dull, weak, dragging, dark, prag- matic, and passive. The tool has been widely used in • Assessment of Dream Experience Scale, which numerous Rogerian studies.

Warfarin provides a (P0) to a fixed mean of three predose measure- good example of this best viagra soft 100mg, as the anticoagulant (hypo- ments, the program can estimate that parameter. Precision increased of compounds emerging from medicinal chemistry when a finite lag time was included in the fitting. These detract from their value in chemical, structure– two cases, however, are especially relevant to the activity analyses). Neither does any of these relationship between animal work and phase I studies approaches uses results of invitro functional assays in which only the simplest effects, such as counter- which emerge from screening of the compounds in action of a painful stimulus or raising/lowering of a biochemistry laboratories. This is a postgraduate textbook, and we wish to convey how in vitro and in vivo data In the future, models will exist which will link of various kinds may be used to help extrapolate constants for in vitro binding to cloned human observed drug effects from simple experimental receptors (Kd), data from in vitro functional assays systems to the more complex clinical situation. The ultimate need is to obtain useful predictions A composite prediction matrix will be applied of response in healthy human subjects (phase I rapidly and accurately to the process of synthesis studies) from observed drug effects in animals or of new compounds for phase I testing. In the shorter term, what can we now do to What are the strengths and weaknesses of these expedite the drug selection process? The use of intrinsic clearance in vitro represents a flow chart illustrating one form of permits predictions between species for the parti- metabolism/pharmacokinetics input into the drug cular enzyme/route of metabolism concerned. Arrows (indicating the flow of humans have qualitatively different routes of work and communication) pointing to the right metabolism for any particular compound, then represent perceived progress, whereas arrows point- this will weaken the predictive value of the in ing tothe leftrepresent ‘disappointments’ (and other vitro observation. The works best for compounds with a high component numbered asterisks indicate continuations. The of nonenzymatic elimination, such as our model ‘flow of time’ is from left to right and from the top compound with approximately 90% excretion as panel to the bottom panel. This prediction weakens as var- tasks that are to be completed, and rectangles in a iations in rates of enzymatic reactions become column within a panel represent work done by more important. If preclinical work identified metabolite(s) to and may not necessarily be based on hard and fast measure in humans, are the pharmacokinetics criteria. Does the relationship between concentration compounds that have the same indication. For example, within the represents the tasks that can be expedited by online box including ‘in vitro intrinsic clearance’, there pharmacokinetic modeling. Among the pharmaco- may be in vitro predictors of oral availability and kinetic questions that will be asked online in the measures of potentially toxic metabolites. The ‘in phase I trial are the following: vivo pharmacokinetics’ in rats may include an increasing number of compartments whose con- 1. As the doses are escalated, do the kinetics of the centrations are measured by microdialysis and may drug appear to be linear or nonlinear over the include measures of a few selected metabolite dose range? However, it does show that the change in kinetics, for example a higher elim- chemists discover new chemical entities with ination rate that might be indicative of autoin- desirable properties. This is not a comprehensive flow diagram for all aspects of drug discovery – it is restricted to the components of the process discussed in this chapter. In this context, phase I serves as the As a chemical series develops, correlations such interface between preclinical research and clinical as that in Figure 8. Eventually, a development, and the validity of the predictions compound or compounds is/are chosen for phase I from animals to humans involved is of paramount studies. In this scheme, phase I is influenced by pharma- We believe that with enhanced integrated study cokinetic and pharmacodynamic modeling. The objective is expe- lism and pharmacokinetics (Welling and Tse, ditious choice of the best compound, with the ever- 1995). The time saved could be used to permit a present limitations on information available. Note larger number of compounds with better pro- that this scheme can involve feedback from phase I spects, from a single research program, to be to renewed chemical synthesis, as well as choice of compared in phase I studies. Typically, after adequate preclinical char- acterization of a candidate drug and 14-day and/or 3-month multiple-dose toxicology studies in two References mammalian species, a very low dose is chosen for the first human exposure to the drug. Doses may be single or short multiple- netics: the dynamics of drug absorption, distribution dose series. PharmacokineticandPha- a-adrenergic receptors and contraction of rat vas rmacodynamic Data Analysis: Concepts and Applica- deferens’. Interspecies scaling and comparisons Pharmacokinetic/Pharmacodynamic Analysis: in drug development and toxicokinetics. Financial pressures, even for the largest pharma- model ceutical companies, are generally much greater than in the past. The technical response is to max- In former times, it was assumed that developmental imize resources, avoiding any and all redundant drugs proceeded in stepwise fashion from phase I, clinical studies. Phase I was conducted in ‘normal volun- the regulatory authorities and from within the teers’ (although some medical students might pharmaceutical companies themselves. After approval, certain stu- earlier stages of drug development when these dies, to find new indications, address special questions are asked, have driven change in patient subpopulations, for marketing purposes or clinical study design. Increasingly sophisticated to otherwise broaden product labeling might or data are now developed at earlier stages of drug might not be conducted. Strategies such as the overlapping of devel- any generally agreed definitions except, perhaps, opment ‘phases’, as well as the use of early dose- that the studies are run by different teams.