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By: David Bruce Bartlett, PhD

  • Assistant Professor in Medicine
  • Member of the Duke Cancer Institute
  • Member of Duke Molecular Physiology Institute

https://medicine.duke.edu/faculty/david-bruce-bartlett-phd

The pupils also normally constrict when a subject shifts focus from the distance to medications gabapentin buy generic combivent 100mcg a near object medications quotes combivent 100 mcg with amex. Disorders of pupillary function Lesions of the pupillary pathways may be broadly classified into afferent and efferent defects medications 4 times a day cheap combivent 100 mcg on-line. Such a relative afferent pupillary defect is an important sign of optic neuritis (Chapter 16) 340b medications buy combivent 100 mcg amex. It is best demonstrated using the swinging torch test, in which light is repeatedly shone into the affected eye alternating with the good side. When it is transferred to the diseased eye, there is bilateral pupillary dilatation. This is because the weak direct reflex on the diseased side is more than counterbalanced by the withdrawal of the stimulus from the normal eye, resulting in consensual dilatation. Abnormalities of pupil size and reactions are frequently encountered in combination with disorders of eye and eyelid movement (see below). Size should be recorded at three ambient light levels: high, intermediate and low. Many normal individuals have pupils that are unequal in size (physiological anisocoria); in this case the difference will be the same at all light levels. When the normal eye is tested (b), its pupil constricts, as does the other pupil consensually. When the torch shines in the unaffected eye (d), there is direct pupillary constriction but no consensual response from the affected eye. The pupil is small and irregular with a preserved near response but reduced or absent light reflex. The superior oblique muscle is supplied by the fourth (trochlear) cranial nerve; lateral rectus by the abducens nerve. All the other muscles are innervated by the oculomotor nerve, which also carries the parasympathetic fibres to the sphincter pupillae, and the nerve 22 Figure 4. When the eye is abducted (a), the superior and inferior rectus muscles are responsible for elevating and depressing the eyeball, respectively. In adduction (b), these actions are taken by the inferior and superior oblique muscles, respectively. Vision and other cranial nerves Chapter 4 supply to levator palpebrae superioris, muscle responsible for elevating the eyelid. The target should inscribe the shape of the letter H in the air, rather than a simple cross, movements in the vertical direction thereby being examined with the eyes both adducted and abducted. Pursuit eye movements tested in this way are the best rapid screening test for disease, as normal pursuit implies the integrity of virtually all the neural pathways involved in the control of eye movement. These tests are important in the distinction between brainstem function and brainstem death in an unconscious patient (Chapter 2). Disorders of eye and eyelid movement Symptoms Patients may be aware of weakness of levator palpebrae superioris from a tendency for the eyelid to droop or close completely (partial and complete ptosis). Diplopia or double vision in neurological practice arises from malalignment of the eyes such that light from an object falls on non-corresponding sites on the two retinae, and the brain is unable to fuse the resultant images. This binocular diplopia, present only when both eyes are open, must be distinguished from monocular diplopia, which persists when one eye is covered. Binocular diplopia arises from an imbalance between the extraocular muscles of the two eyes or of their innervation.

These growth factors professional english medicine cheap combivent 100mcg without prescription, the hematopoietic cytokines treatment writing order combivent 100 mcg without prescription, are identified by their ability to treatment jokes buy combivent 100 mcg lowest price stimulate the formation of hematopoietic cell colonies in bone-marrow cultures medicine ball slams discount combivent 100 mcg free shipping. Produced by the kidney, this cytokine induces the terminal development of erythrocytes and regulates the production of red blood cells. Further studies showed that the ability of a given cytokine to signal growth and differentiation is dependent upon the presence of a receptor for that cytokine on the surface of the target cell-commitment of a progenitor cell to a particular differentiation pathway is associated with the expression of membrane receptors that are specific for particular cytokines. Many cytokines and their receptors have since been shown to play essential roles in hematopoiesis. Adherent bone-marrow stromal cells form a matrix on which the hematopoietic cells proliferate. Single cells can be transferred to semisolid agar for colony growth and the colonies analyzed for differentiated cell types. The proteins specified by these genes are critical components of regulatory networks that direct the differentiation of the stem cell and its descendants. Much of what we know about the dependence of hematopoiesis on a particular gene comes from studies of mice in which a gene has been inactivated or "knocked out" by targeted disruption, which blocks the production of the protein that it encodes (see Targeted Disruption of Genes, in Chapter 23). If mice fail to produce red cells or particular white blood cells when a gene is knocked out, we conclude that the protein specified by the gene is necessary for development of those cells. Knockout technology is one of the most powerful tools available for determining the roles of particular genes in a broad range of processes and it has made important contributions to the identification of many genes that regulate hematopoiesis. Although much remains to be done, targeted disruption and other approaches have identified a number of transcription factors (Table 2-1) that play important roles in hematopoiesis. Some of these transcription factors affect many different hematopoietic lineages, and others affect only a single lineage, such as the developmental pathway that leads to lymphocytes. As might be expected, animals in which this gene is disrupted die during embryonic development. Ikaros knockout mice survive embryonic development, but they are severely compromised immunologically and die of infections at an early age. Hematopoietic Homeostasis Involves Many Factors Hematopoiesis is a continuous process that generally maintains a steady state in which the production of mature blood cells equals their loss (principally from aging). The average erythrocyte has a life span of 120 days before it is phagocytosed and digested by macrophages in the spleen. To maintain steady-state levels, the average human being must produce an estimated 3. Hematopoiesis is regulated by complex mechanisms that affect all of the individual cell types. These regulatory mechanisms ensure steady-state levels of the various blood cells, yet they have enough built-in flexibility so that production of blood cells can rapidly increase tenfold to twentyfold in response to hemorrhage or infection. For example, abnormalities in the expression of hematopoietic cytokines or their receptors could lead to unregulated cellular proliferation and may contribute to the development of some leukemias. Ultimately, the number of cells in any hematopoietic lineage is set by a balance between the number of cells removed by cell death and the number that arise from division and differentiation. Any one or a combination of regulatory factors can affect rates of cell reproduction and differentiation. Cells undergoing programmed cell death often exhibit distinctive morphologic changes, collectively referred to as apoptosis (Figures 2-3, 2-4). Following these morphologic changes, an apoptotic cell sheds tiny membrane-bounded apoptotic bodies containing intact organelles. Macrophages quickly phagocytose apoptotic bodies and cells in the advanced stages of apoptosis. This ensures that their intracellular contents, including proteolytic and other lytic enzymes, cationic proteins, and oxidizing molecules are not released into the surrounding tissue. Apoptosis differs markedly from necrosis, the changes associated with cell death arising from injury. In necrosis the injured cell swells and bursts, re- leasing its contents and possibly triggering a damaging inflammatory response. Each of the leukocytes produced by hematopoiesis has a characteristic life span and then dies by programmed cell death. In the adult human, for example, there are about 5 1010 neutrophils in the circulation.

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Most patients present with constitutional symptoms and involvement of the kidneys symptoms high blood pressure discount combivent 100 mcg with mastercard, gastrointestinal tract or muscles; in a minority there may be a peripheral neuropathy medicine 72 purchase combivent 100 mcg visa, and in a smaller minority medicine sans frontiers order 100mcg combivent otc, central nervous system involvement treatment yersinia pestis 100 mcg combivent with mastercard, with stroke, delirium, or dementia. Course the disease is progressive and, once renal involvement occurs, death may follow within months. Etiology Within the central nervous system, several different pathologies may be found (Drachman 1963, Nishino et al. Small, or rarely large, vessels may undergo a vasculitis and, with occlusion, infarction occurs. Granulomas may be found, and these may appear by extension from an extracranial source. Granulomatous involvement of the meninges, primarily the pachymeninges, may also occur, and cranial nerves may be entrapped and compressed; cranial neuropathies may also occur due to compression of the cranial nerves in their extracranial portions by extracranial granulomas. Treatment Treatment with corticosteroids and cyclophosphamide is recommended; consideration may also be given to antiplatelet agents (Reichart et al. The nervous system is involved in a minority of cases: peripheral neuropathy is the most common manifestation; within the central nervous system there may be a vasculitis, intracerebral granulomas, and, rarely, a pachymeningitis. Clinical features Over 90 percent of patients have symptoms referable to granulomas within the respiratory tract. Upper respiratory tract involvement is most common, with sinusitis, epistaxis, or rhinorrhea; involvement of the nasal septum may lead to its collapse, and extension of granulomatous disease to the orbit may cause proptosis. Some three-quarters of patients will have renal involvement, which may manifest initially with proteinuria and microscopic hematuria. Nervous system involvement generally occurs in the context of respiratory or renal symptomatology (Hoffman et al. Clinical evidence of a mononeuritis multiplex or polyneuropathy is seen in about one-third of patients (de Groot et al. Magnetic resonance scanning will reveal intracerebral granulomatous lesions, infarcts, and meningitis. The cerebrospinal fluid may be normal or may show a lymphocytic pleocytosis and an elevated total protein. Treatment In most cases, treatment with a combination of prednisone and cyclophosphamide is required. Other symptoms include furuncles, erythema nodosum, migratory thrombophlebitis, and a non-deforming polyarthritis. Within the context of these symptoms evidence of central nervous system involvement may appear. When the central nervous system is involved, a wide variety of symptoms may appear (Akman-Demir et al. These include delirium, dementia, pseudobulbar palsy with emotional incontinence (Pallis and Fudge 1956; Motomura et al. As noted below, in addition to vasculitis, both meningitis and dural sinus thrombosis may occur, and in such cases one may see headache; in cases of dural sinus thrombosis, one may also see signs of increased intracranial pressure, with nausea, vomiting, and papilledema. Magnetic resonance venography may be required to demonstrate dural sinus thrombosis. Etiology A perivenular vasculitis occurs and, although this may be seen in any part of the central nervous system, there is a predilection for the pons, mesencephalon and diencephalon, the cerebellum, and, to a lesser degree, the frontal lobes. Meningeal inflammation may also occur, which may be accompanied by dural sinus thrombosis. Although the etiology is not known, an autoimmune process is suspected; the vast majority of cases are sporadic. Treatment During attacks patients should be treated with prednisone and an immunosuppressant. Before proceeding, some words are in order regarding the syndrome known as reversible posterior leukoencephalopathy. The first attack, as noted, tends to occur in the 20s or 30s, and most attacks last in the order of weeks or a month or more, after which there is a spontaneous remission. These remissions, however, are generally not complete, and most patients are left with residual symptoms. Recurrent attacks are the rule, and after each attack the overall burden of residual symptoms increases.

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A) Telomeres are repetitive nucleotide sequences at the end of a chromatid B) Telomeres serve as protective caps that prevent the chromosome from deterioration during cell division C) Telomeres are gradually consumed during repeated cell divisions D) In cancer cells symptoms lyme disease generic 100mcg combivent with amex, telomerase activity is usually reduced compared with normal cells 5 medications high blood pressure buy 100 mcg combivent visa. A) Condensation of the chromosomes B) Replication of the genome C) Fragmentation of the nuclear envelope D) Alignment of the chromatids along the equatorial plate E) Separation of the chromatids into two sets of 46 "daughter" chromosomes 6 medications overactive bladder trusted combivent 100mcg. The abnormal cleavage of mannose residues during the post-translational processing of glycoproteins results in the development of a lupus-like autoimmune disease in mice medications similar to cymbalta purchase 100mcg combivent with amex. The observation that abnormal cleavage of mannose residues from glycoproteins causes an autoimmune disease in mice supports the role of this structure in the normal immune response. Studies completed on a 5-year-old boy show an accumulation of cholesteryl esters and triglycerides in his liver, spleen, and intestines and calcification of both adrenal glands. Additional studies indicate the cause to be a deficiency in acid lipase A activity. A) Autophagosomes B) Granular endoplasmic reticulum C) Agranular endoplasmic reticulum D) Golgi apparatus E) Mitochondria 15. A) Synthesis of lipids B) Synthesis of proteins C) Providing enzymes that control glycogen breakdown D) Providing enzymes that detoxify substances that could damage the cell E) Secretion of proteins synthesized in the cell 16. Which of the following does not play a direct role in the process of transcription? Which of the following proteins is most likely to be the product of a proto-oncogene? A) Proto-oncogenes are normal genes that code for proteins that control cell growth B) Proto-oncogenes are normal genes that code for proteins that control cell division C) Inactivation of anti-oncogenes protects against the development of cancer D) Several different simultaneously activated oncogenes are often required to cause cancer 20. A) Most control systems of the body act by negative feedback B) Positive feedback usually promotes stability in a system C) Generation of nerve actions potentials involves positive feedback D) Feed-forward control is important in regulating muscle activity 2 Unit I Introduction to Physiology: the Cell and General Physiology 21. Assume that excess blood is transfused into a patient whose arterial baroreceptors are nonfunctional and whose blood pressure increases from 100 to 150 mm Hg. Then, assume that the same volume of blood is infused into the same patient under conditions in which his arterial baroreceptors are functioning normally and blood pressure increases from 100 to 125 mm Hg. What is the approximate feedback "gain" of the arterial baroreceptors in this patient when they are functioning normally? A) Endoplasmic reticulum B) Mitochondria C) Lysosomes D) Golgi apparatus E) Peroxisomes F) Ribosomes 23. D) the extracellular fluid has relatively high concentrations of sodium and chloride ions but lower concentrations of potassium and phosphate compared with the intracellular fluid. C) the variation in proteins expressed by each cell reflects cell-specific expression and repression of specific genes. D) Telomeres are repetitive nucleotide sequences, located at the end of a chromatid, that serve as protective caps to prevent the chromosome from deterioration during cell division, but they are gradually consumed during cell divisions (see figure below). In cancer cells, the enzyme telomerase is activated (not inhibited) and adds bases to the ends of the telomeres so that many more generations of cancer cells can be produced. The chromatids align at the equatorial plate during metaphase and separate into two complete sets of daughter chromosomes during anaphase. B) the cell "glycocalyx" is the loose negatively charged carbohydrate coat on the outside of the surface of the cell membrane. The membrane carbohydrates usually occur in combination with proteins or lipids in the form of glycoproteins or glycolipids, and the "glyco" portion of these molecules almost invariably protrudes to the outside of the cell. B) the term homeostasis describes the maintenance of nearly constant conditions in the internal environment of the body, and diseases are generally considered to be states of disrupted homeostasis. However, even in diseases, homeostatic compensatory mechanisms continue to operate in an attempt sustain body functions at levels that permit life to continue. These compensations may result in deviations from the normal level of some body functions as a "trade-off " that is necessary to maintain vital functions of the body. E) Membrane proteins are glycosylated during their synthesis in the lumen of the rough endoplasmic reticulum.

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References:

  • https://www.pnas.org/content/pnas/97/18/10173.full.pdf
  • https://pmj.bmj.com/content/postgradmedj/81/956/383.full.pdf
  • https://www.ojp.gov/pdffiles1/Digitization/110929NCJRS.pdf
  • https://www.henryschein.com/assets/Medical/1176307.pdf