By G. Goran. Northwest University. 2019.
Segmentation aides in the physical breakdown of ingested foods buy clomid 100 mg overnight delivery breast cancer ribbon tattoo, the mixing of the luminal contents with enzymes for more efficient processing trusted 50mg clomid women's health clinic orlando, and the elimination of waste purchase cheapest clomid and clomid pregnancy depression. The mixing motility pattern blends pancreatic, biliary, and intestinal secretions with chyme arriving from the stomach and brings digestive products into contact with the absorptive surfaces of the mucosa. Peristalsis is one of the contractions that occur during and shortly after a meal. The muscle layers of the intestine behave in a characteristic pattern during peristaltic propulsion (Fig. As part of the first component of peristaltic propulsion, the longitudinal muscle in the segment ahead of the advancing intraluminal contents contracts at the same time the circular muscle layer relaxes, which results in expansion of the lumen and prepares a receiving segment for the forward-moving intraluminal contents. The second component is contraction of the circular muscle in the segment behind the advancing intraluminal contents with a simultaneous contraction of the longitudinal muscle layer, which converts this region to a propulsive segment that propels the luminal contents forward into the receiving segment. The process of lengthening in the longitudinal axis in the propulsive segment is unclear. Connections for these reflexes remain, irrespective of the destruction of adjacent regions of the spinal cord. In the same way that the monosynaptic reflex circuit of the spinal cord is the terminal circuit for the production of almost all skeletal muscle movements (see Chapter 5), the basic peristaltic reflex circuit of synaptic connections underlies all patterns of propulsive motility. Blocks of the same basic circuit are connected in series up and down the intestine (Fig. Distances over which peristaltic propulsion travels are determined by the number of blocks recruited in sequence along the bowel. Synaptic gates between the blocks determine whether recruitment occurs for the next circuit in the sequence. When the gates are opened, neural signals pass between successive blocks of the basic circuit, resulting in propagation of the peristaltic event over extended distances. Transmission at the synapses opens the gates between successive blocks of the basic peristaltic reflex circuit and accounts for propagation of peristaltic propulsion over long distances. Presynaptic inhibition and/or facilitation are involved in gating the transfer of signals between sequential blocks. Synapses between the neurons that carry excitatory signals to the next block are gating points for control of the distance over which peristaltic propulsion travels (Fig. Inhibitors of transmitter release at excitatory synapses close the gates to the transfer of information, thereby determining the distance of propagation. Prokinetic drugs that facilitate the release of neurotransmitters at the excitatory synapses (e. In the absence of presynaptic inhibition, propagation can proceed in the direction in which the gates are open. Activation of presynaptic inhibitory receptors closes the gates and no propagated propulsion can occur. Emesis Vomiting (emesis) is the forceful expulsion of the stomach contents out through the mouth and may result from several causes, ranging from gastritis, food poisoning, binge drinking, brain tumors, and brain trauma. Although the terms “vomiting” and “regurgitation” are often used interchangeably, they are different. Regurgitation is the return of undigested food back up the esophagus without the forced expulsion associated with vomiting and occurs most commonly in neonates. If forward passage of the intraluminal contents is impeded in the large intestine, reverse propulsion propels the bolus over a variable distance away from the obstructed segment. Retropulsion then stops and forward propulsion moves the bolus again in the direction of the obstruction. In both cases, the musculature for propulsion is stimulated to contract in the reverse direction. Esophageal motility involves contraction of striated muscle in the upper esophagus and smooth muscle in the lower third of the esophagus. The esophagus transports ingested solids and liquids downward from the pharynx to the stomach during a swallow and upward during expulsion of gastric contents (i. Voluntary muscle contraction in the oral cavity moves the bolus posteriorly and into the pharynx. After swallowing, the transit time through the pharynx and esophagus is about 6 to 10 seconds (Clinical Focus 27. Dysphagia limited to solid food is most often a symptom of a mechanical obstruction (e. Some dysphagic patients have pressure waves of abnormally high amplitude as peristalsis propagates past the recording ports during diagnostic assessment with manometric catheters. This condition, which is called nutcracker esophagus, is often associated with angina-like chest pain. A manometric diagnosis of nutcracker esophagus is usually made subsequent to confirmation that the patient’s chest pain does not reflect blockages in the coronary arteries. A diagnosis of achalasia is made when manometric recording of esophageal motility fails to show the typical relaxation and reduction of intraluminal pressure in the sphincter coincident with the onset of a swallow (see Fig. Successful therapy involves mechanical dilation of the sphincter either by pneumatic inflation of a balloon placed in the sphincter or by passage of a solid bougie dilator. A class of smooth muscle relaxant drugs, known as phosphodiesterase-5 inhibitors (e. Achalasia, in the majority of cases, reflects the loss of the enteric inhibitory motor innervation of the sphincter. In paraneoplastic syndrome, antigens expressed by a carcinoma (usually small cell carcinoma) in the lung have sufficient similarity to antigenic epitopes expressed by enteric neurons that the immune system simultaneously attacks the tumor and the patient’s enteric neurons. Most patients with a diagnosis of achalasia, in combination with small cell lung carcinoma, have circulating immunoglobulin-G autoantibodies that react with and destroy their enteric neurons. The detection of antienteric neuronal antibodies is a supplemental means to a specific diagnosis of achalasia. Trypanosoma cruzi, the blood-borne parasite that causes Chagas disease, has antigenic epitopes similar to enteric neuronal antigens. When chest pain is associated with liquid and solid food dysphagia in the absence of nutcracker- like contractions, the problem is most likely a form of failure of peristaltic propulsion, called diffuse esophageal spasm. A diagnosis of diffuse spasm is made when manometric recording of esophageal motility demonstrates that the act of swallowing results in simultaneous contractions all along the length of the smooth muscle region of the esophageal body. A barium study in patients with diffuse spasm shows the morphometric correlate of diffuse spasm to be a contorted esophageal body, which has been described as a “corkscrew esophagus. There are no fully satisfactory treatments for diffuse spasm other than attempts to treat with smooth muscle relaxant drugs. Secondary peristalsis is a subconscious process that is triggered by distention associated with failed downward transport (i. Secondary peristalsis accompanied by the stimulation of salivary secretion is the normal mechanism for “dislodging” the bolus as well as removing acid irritation. In contrast to the intestine, the relaxed state of the esophageal body is not the result of inhibitory motor neuron activity. Activation of excitatory motor neurons, rather than myogenic mechanisms, accounts for the coordinated contractions of the circular and longitudinal muscles during peristaltic propulsion. Large- amplitude muscle contractions are associated with each slow wave when action potentials are present.
Thus current builds up a potential dif of (but insulated from) the primary wind ference between the two ends of the coil 25mg clomid free shipping women's health issues pregnancy week by week, ings cheap clomid online american express women's health center in newport news va. As soon as the magnetic feld stabi iron alloys separated from each other by lizes generic clomid 50mg line breast cancer in men symptoms, the potential across the secondary coil thin insulating layers. These sheets are drops to zero and remains there until the clamped tightly together. When the laminations is to reduce eddy currents, the switch is opened, the magnetic feld de which waste power and appear as heat in creases, and again this changing feld in the transformer core. The voltage In the two circuits is proportional is reversed, and the voltmeter needle to the number of turns in the two coils. The volt age across the primary coil is shown in Fig ure 3-1B, and that across the secondary coil in Figure 3-1C. No cur V, = voltage in the secondary circuit rent fows while the magnetic feld is stable. For example, suppose the primary coil For this reason, steady direct current (like has 100 turns and the secondary coil has that from a battery) in the primary coil can 30,000 turns. If the potential difference not be used to produce a continuous cur across the primary coil is 100 V, the poten rent through the secondary coil. Current fows in one and direction while the voltage is positive and in the opposite direction while the voltage v, = 30,000 v is negative. The most important character A transformer with more turns in the sec istic of alternating current is that its voltage ondary coil than in the primary coil in changes continuously, so it produces a con creases the voltage of the secondary circuit tinuously changing magnetic feld. There and, appropriately, is called a step-up fore, an alternating current in the primary transformer. One with fewer turns in the coil of a transfer produces an alternating secondary coil decreases the voltage and is current in the secondary coil. The second law of transformers is simply a re Laws of Transformers statement of the law of the conseration of en ergy. An Two simple laws govern the behavior of increase in voltage must be accompanied by a a transformer. If the current in the primary coil is 30 A, then the current in the secondary coil will be 100 X 30 = 30,000I, Figure 3-2 Alternating current wave form I, = 0. If the potential difference is in volts ament circuit and the current is in amperes, then power Provides voltage for the primary of will be in watts: the high-voltage transformer Provides suitable voltage for subsidi W = V X I W =watts ary circuits, which we will not con V =volts sider I = amperes Provides a convenient location for the kVp meter that indicates the volt In the last example the power in the trans age to be applied across the x-ray former is 3,000 W; it is the same on both tube the high-voltage (100 V x 30 A) and low An autotransformer consists of a single voltage (30,000 V x 0. The autotransformer works on must be large enough to carry the current the principle of self-induction. As a result, high-volt nating current applied between the input age transformers are both large and heavy, points (A and B, Fig. This In summary, a step-up transformer in magnetic fux will link with all the turns creases the voltage and decreases the cur forming the coil, inducing a voltage into rent, while a step-down transformer de each turn of the winding. For example, if creases the voltage and increases the 230 V are applied between points A and B current. One circuit contains the step-up transformer and supplies the high voltage to the x-ray tube. The other circuit contains a step-down transformer and sup plies the power that heats the flament of the x-ray tube. A transformer called the "autotransformer" supplies the primary voltage for both these circuits. In Figure 3-3, a connection proximately 10 to 20 times as many turns between terminals 0 and P will tap 115 of wire in the primary coil as in the sec turns and supply 230 V There are only 55 ondary coil. The secondary winding of the turns and 110 V between terminals 0 and flament transformer has only a very small X, while 160 turns provide 320 V Notice voltage across it, and is connected to the that, within a very limited range, an auto filament of the x-ray tube. The x-ray tube, transformer can function as a step-up or of course, has a very high voltage across it. This makes it necessary to provide high We will discuss the specific connections voltage insulation between the secondary from the autotransformer (flament circuit, and primary windings of the flament high tension transformer primary, kVp transformer. The flament circuit regulates current Precise control of flament heating is fow through the flament of the x-ray tube critical, because a small variation in fla (Fig. The flament is a coiled tungsten ment current results in a large variation wire that emits electrons when it is heated in x-ray tube current. Remember that x by this current fow (thermionic emission, ray tube current is produced by the fow explained in Chapter 2). Not much power of electrons from their point of origin (the is needed to heat this filament to the nec flament) to the anode (target) of the x-ray essary high temperature; a current flow of tube. A change is flament voltage of about 3 to 5 A with an applied voltage of about 5% will result in a 20- to 30-% change in 10 V are typical values. The x-ray filament cur heats the flament, and does not represent rent may be controlled by altering the volt the current across the x-ray tube. The primary winding of the fila may be a single variable resistor as shown ment transformer obtains its voltage by in Figure 3-4. If resistance is increased, tapping off an appropriate number of more voltage must be used to push current turns from the autotransformer (Fig. For example, a current of 4 A and a to the desired 10 V range, the step-down resistance of 1. There is also a circuit that automatically Figure 3-4 Filament circuit compensates for the space charge effect. The potential difference across the cuits could be shown in Figure 3-4 as boxes secondary coil may be as high as 150,000 in the circuit between the autotransformer V, so the step-up transformer is immersed and the flament transformer, but we in oil in the transformer assembly for max choose to refrain from drawing them. Two meters are incorporated into the High-Voltage Circuit high-voltage circuit, one to measure kVp A simplifed schematic of the high-volt and the other to measure rA. The meters age (cathode-anode) circuit is shown in Fig themselves are located on the control ure 3-5. The circuit has two transformers, panel, but their connections are in the an autotransformer and a step-up trans high-voltage circuit, as shown in Figure former. The autotrans x-ray tube and the actual current fowing former is actually the kVp selector and is through the tube during an x-ray expo located in the control panel. A voltmeter measures the difference across the primary coil of the step-up trans in electrical potential between two points. Only fve selections are shown In a closed circuit, the same number of in Figure 3-5, but actually the kVp can be electrons fows through all points. An am adjusted in steps from approximately 40 to meter counts the number of electrons fow 150 kVp. Some voltage is lost in the Rectifcation rectifer circuit, but with the appropriate Rectifcation is the process of changing calibrations the potential difference in the alternating current into direct current, high-voltage side of the circuit (i. The simplest way to use this the circuit between the autotransformer high voltage is to hook an x-ray tube di and step-up transformer, as shown in Fig rectly to the secondary windings of the ure 3-5.
This treatment involves inserting metal rods through the length of the long bones to strengthen them and prevent and/or correct deformities buy clomid 50 mg with amex women's health clinic in rockford il. Explain how castration causes a large increase in luteinizing hormone levels and why testosterone replacement does not completely correct follicle-stimulating hormone levels order clomid 100 mg free shipping women's health center syracuse ny. Explain how the pampiniform plexus and cremasteric muscle maintain testes at a cooler temperature purchase clomid 100 mg amex women's health clinic gwinnett county. Explain how mitosis, meiosis, and spermiogenesis mechanistically coordinate the continuous production of fresh spermatozoa. Explain how the spermatozoon’s head, middle piece, and tail mechanistically function to reach, recognize, and fertilize an egg. Explain how normal spermatogenesis almost never occurs with defective steroidogenesis, but normal steroidogenesis can be present with defective spermatogenesis. The reproductive system is designed solely for the purpose of survival of the species. Although the reproductive system does not contribute to homeostasis and individual survival, it still plays an important role in physiology and behavior. The reproductive system includes the gonads, reproductive tract, and accessory glands. The overall function of male reproduction is the production of sperm and delivery of the sperm to the female. The testes produce mature male gametes, known as spermatozoa, which function to fertilize the female counterpart, the oocyte, during conception. This fertilization, in turn, produces a single-celled individual known as a zygote. The system is divided into factors affecting male reproductive function: brain centers, which control pituitary release of hormones and sexual behavior; gonadal structures, which produce sperm and hormones; a ductal system, which stores and transports sperm; and accessory glands, which support sperm viability. The endocrine glands of the male reproductive system include the (1) hypothalamus, (2) anterior pituitary, and (3) testes. Leydig cells reside in the interstitium of the testes, between seminiferous tubules, and produce testosterone. Glycosylation regulates the half-life, protein folding for receptor recognition, and biologic activity. These factors activate the promoter region of the genes of steroidogenic enzymes that control testosterone production by Leydig cells. Similar signaling occurs in Sertoli cells that regulate the production of estradiol. The testis converts testosterone and some other androgens to estradiol by the process of aromatization, although estradiol production is low in males. Another major function of the testis is the production of mature sperm and of several regulatory proteins (activin, androgen-binding protein, follistatin, and inhibin), characteristics of which are detailed in later sections. Inhibin is composed of two dissimilar subunits, α and β, which are held together by disulfide bonds. Inhibin B consists of the α subunit bound by a disulfide bridge to the βB subunit and is the physiologically important form of inhibin in the human male. The major form of activin in the male is currently unknown, although both Sertoli and Leydig cells have been implicated in its secretion. Follistatin is a single-chain protein hormone, with several isoforms, that binds and deactivates activin. Follistatin is produced by Sertoli cells and acts as a paracrine factor on the developing spermatogenic cells. During embryonic stages of development, the testes lie attached to the posterior abdominal wall. Between the seventh month of pregnancy and birth, the testes descend through the inguinal canal into the scrotum. The location of the testes in the scrotum is important for sperm production, which is optimal at 2°C to 3°C lower than the core body temperature. One is the pampiniform plexus of blood vessels, which serves as a countercurrent heat exchanger between warm arterial blood reaching the testes and cooler venous blood leaving the testes. The second is the cremasteric muscle, which responds to changes in temperature by moving the testes closer or farther away from the body. Prolonged exposure of the testes to elevated temperature, fever, or thermoregulatory dysfunction can lead to temporary or permanent sterility as a result of a failure of spermatogenesis, whereas steroidogenesis is unaltered. A thick, fibrous connective tissue layer, the tunica albuginea, encapsulates the testes. Each human testis contains hundreds of tightly packed seminiferous tubules, ranging from 150 to 250 μm wide and from 30 to 70 cm long. The tubules are arranged in lobules, separated by extensions of the tunica albuginea, and open on both ends into the rete testis. Examination of a cross-section of a testis reveals distinct morphologic compartmentalization. Each seminiferous tubule is composed of two somatic cell types (myoid cells and Sertoli cells) and germ cells. A basement membrane (basal lamina) with myoid cells on its perimeter, which define its outer limit, surrounds the seminiferous tubule. On the inside of the basement membrane are large, irregularly shaped Sertoli cells, which extend from the basement membrane to the lumen (Fig. The tight junctions divide each tubule into a basal compartment, whose constituents are exposed to circulating agents, and an adluminal compartment, which is isolated from blood-borne elements. The tight junctions limit the transport of fluid and macromolecules from the interstitial space into the tubular lumen, forming the blood–testis barrier. This cross-sectional view shows the anatomic relationship of the Leydig cells, basement membrane, seminiferous tubules, Sertoli cells, spermatogonia, and spermatozoa. Sertoli cells are connected by tight junctions, which divide the intercellular space into a basal compartment and an adluminal compartment. Spermatogonia are located in the basal compartment and maturing sperm in the adluminal compartment. Spermatocytes are formed from the spermatogonia and cross the tight junctions into the adluminal compartment; they mature into spermatozoa. Located between the nonproliferating Sertoli cells are germ cells at various stages of division and differentiation. Mitosis of the spermatogonia (diploid progenitors of spermatozoa) occurs in the basal compartment of the seminiferous tubule (see Fig. The early meiotic cells (primary spermatocytes) move across the junctional complexes into the adluminal compartment, in which they mature into spermatozoa or gametes after meiosis. The adluminal compartment protects spermatozoa from the immune system that does not recognize spermatozoa that develop in the adluminal compartment as “self. Sperm antibodies are often present after vasectomy or testicular injury and in some autoimmune diseases in which the adluminal compartment is ruptured. Sertoli cells are critical to germ cell development, as indicated by their close contact. Sertoli cells phagocytose residual bodies (excess cytoplasm resulting from the transformation of spermatids to spermatozoa) and damaged germ cells, provide structural support and nutrition for germ cells, secrete fluids, and assist in spermiation-the final detachment of mature spermatozoa from the Sertoli cell into the lumen. Spermiation may involve plasminogen activator, which converts plasminogen to plasmin, a proteolytic enzyme that assists in the release of the mature sperm into the lumen.
There should be an apex State level nutrition tuted with the sectoral representatives or administrators council to be chaired by the Chief Minister and essential for decision making on policy matters discount clomid 100 mg mastercard womens health personal trainer. The Committee would also focus on Ministers generic 50 mg clomid mastercard menopause the musical chicago, a few State Ministers by rotation and experts the State level targets for the various nutrition related and representatives of nongovernmental organizations cheap 50 mg clomid amex breast cancer 5k atlanta 2014. The The Council will be the national forum for policy Secretary of the Department dealing with women and coordination, review and direction at the national level. The National Special working groups will be set in the Nutrition Council will be the highest body for Departments of Agriculture, Rural Development, Health, overseeing the implementation of the National Nutrition Education, Food and Women and Child Development Policy through the various sectoral plans of action and and these group will be responsible for vetting the will issue policy guidelines based on latest nutritional various sectoral schemes from the point of view of surveillance feedback. It is all parts of the country is a definite obstacle towards a possible to replicate these examples. The other State Governments/ and to develop a mechanism for generating nationwide Union Territory Administration may also consider such an disaggregated data within a short period for use by the introduction in their primary and secondary schools. The Central and the States for taking corrective action wher- private schools and schools which are capable of mobilizing ever necessary. This would ensure a regular monitoring their own resources may be encouraged to introduce such and surveillance system and develop a reliable data base schemes out of their own resources. State Coordination Committees and as an early warning system for initiating prompt action. Manual of Child Health and October, commemorating the founding of the Food Nutrition. The Assessment of the Nutritional Status of the awareness of the world food problem, hunger, Community. A Joint Statement by References the World Health Organization and the United Nations Children’s Fund. London: Taylor and Francis, Organised by Food and Nutrition Board, Deptt of Food, 1985. Effect of Giardia Infection on Nutritional the Indian Council of Medical Research, 2010. Published by Roussel Assessment of iodine deficiency disorders in Purulia District, Scientific Institute, India, 1988. Iodine deficiency disorders among school children New Delhi: Century Publications, 1999. Iron absorption and its implications on strategies to Iodisation Level in a District of West Bengal, India. Even before the Sources of Data observations are made and data collected, experiments have to be designed and surveys planned keeping in • Experiments performed in the laboratory or in the mind the subsequent statistical analysis of data. It is strongly recommended that the more serious The figures from the above sources are obtained student should read an appropriate textbook suitable either by measurement or by enumeration. The tabulating numerical data and expressing the results in data collected by counting are called discrete data, e. Biostatistics is that the number of persons dying or cured of a particular branch of statistics concerned with mathematical facts disease. Continuous data are numerically measurable, and data relating to biological events. The term continuous is a further specialty of biostatistics when the mathe- indicates that there is no natural demarcation between matical facts and data are related to health, preventive different categories. Vital statistics is that branch of and 166 cm tall respectively, but there may be persons statistics that deals mainly with births, deaths, human 165. Presentation of statistics, Variability and error, Analysis and interpre- Different Scales of Measurement tation of data, Sampling, Sampling variations and Tests of significance. Here data is divided into qualitative categories or group • To evaluate the efficacy of vaccines, sera, etc. For example, male/female, urban/rural, right/left, yes/no and 0/1 are examples of Presentation of Statistics nominal data. Among the measures of central tendency, only mode can be applied over nominal scale. Chi- After the data has been collected, it has to be sorted square test is the most common test of statistical out and presented properly for analysis and significance that can be utilized in this scale. We can not say (very severe disease – vations is large and several attributes have to be studied, severe pneumonia = pneumonia – no pneumonia). For example, postgraduate Thus ordinal scale only permits ranking of items from medical students have to prepare a master table or highest to lowest. But this scale does not have absolute zero (an This is the most important table in statistical work. In arbitrary zero point is assigned), so 100°C in not equal a frequency table large, unsorted data is presented in to twice 50°C (100°C ≠ 2 × 50°C). It records how not indicate complete absence of heat, rather it is the frequently a characteristic occurs in persons of the same freezing point of water. Only temperature scale that follows Frequency Distribution Table of interval scale is Kelvin scale. Therefore, it is correct to say that a pulse rate of 120 is twice as fast as pulse rate An example would be a table for height of 100 boys, of 60. The number of boys in a particular range is recorded against each height category. The Line Chart or Graph categories showing the range of the variable should It shows the trend of an event over a period of time. The trend may indicate rise, fall or fluctuations in The following three points should be kept in mind occurrence of the event. Examples are graphs showing while making such a table: incidence of cancer, infant mortality, births, deaths, etc. If the data are expressed in rates or proportions, this Bar Diagram should be specified. If some data are omitted, the The length of the bar indicates the frequency, which is reason should be explained. The character of different groups is indicated on the horizontal axis or abscissa, while frequency is indicated on the vertical axis or ordinate. The heights of frequency rectangles vary and the area of a rectangle represents the frequency. Such a diagram is called histogram and is made use of in presenting quantitative data (such as of height in the frequency Table 23. Frequency Polygon It is simply a derivation from the histogram obtained by joining the midpoints of various histogram blocks. The space between any A graphic presentation is made here to show the extent two bars should prevalence rate per 1000 population, and nature of correlation between two variables such 1974 to 1978 be so adjusted that the presentation may as height and weight, hence it is also called a ‘correlation appear neat, clean and easily comprehensible. Two dots of two different colors on the map of a country may show two different characteristics, such Fig. The relative new and repeat outdoor attendance frequency of a disease may also be indicated by different marks such as O, X, + and –, etc.
These pathologies are not static but may evolve with time purchase clomid in india women's health magazine healthy skin tips, be- ing modified by other pathophysiological parameters buy clomid 25 mg otc menstruation ovulation period, and therefore windows of ther- apeutic intervention may be achievable buy clomid 25 mg with amex womens health usa. The anatomy and physiology of the child, particularly the very young child, are different from those of the adult, and thus the tissue responses are often different. Long- term neurodegeneration is more frequent after traumatic brain injury, but to date we do not know how to identify patients at risk and the underlying pathological processes. London, cranial hematomas, in Handbook of Clinical Neurology, Vol Arnold, 1997, pp 197–262 15: Head Injury. Amsterdam, Lindenberg R: Trauma of the meninges and brain, in Pathology of Elsevier, 1990, pp 249–298 the Nervous System. Neuropathol Appl Neurobiol 26:448–453, 2000b thology and Genetics: Cerebrovascular Disease. Neuroscience 136:971–989, 2005 changes are an early consequence of repetitive head injury. For exam- ple, in clinical practice one can see very different cogni- tive and functional outcomes in individuals with similar An array of genetic responses is triggered by neurotrauma preinjury intellectual and educational backgrounds and both acutely and over time (DeKosky et al. Since genes (thought to play a role in promoting transcription of the 1970s the field has progressed from counting the num- other genes that in turn facilitate initiation of excitotoxic ber of chromosomes or identifying structural deficits in cascades) (Dutcher and Michael 2001; Michael et al. The Appendix provides brief definitions 3) preinjury traits and cognitive capacities, 4) links to neu- of key terms and concepts with which it is helpful to be fa- robehavioral disorders (see Figure 3–1). Individuals less familiar broad categories involve multiple steps (and hence multi- with this area may find it useful to review the Appendix ple genes) and thus are under complex polygenic control. For additional details the reader is referred to texts For example approximately 75–100 genes have been iden- such as Human Molecular Genetics (Strachan and Read tified as candidates for affecting human cognition (Morley 2004). Even in conditions in which signif- in this chapter is not to provide an exhaustive list of po- icant associations have been found between the condition tential candidate genes and alleles (see Jordan 2007 for re- or trait and a given gene or allele, the effect size is typically view), but rather to illustrate the various ways that genetic small, accounting for 1%–5% of the variance (Comings differences influence response to trauma and provide il- 1998). Although the individual contribution of a given al- lustrative examples of mechanisms that may inform treat- lele might be small, the effects of multiple alleles could be ment in the future. Excessive Functional outcome release of these compounds has been associated with neu- – Cognition ronal death (see DeKosky et al. Scheme of potential mechanisms for two broad classes of receptor families: ionotropic and me- genetic modulation of outcome after traumatic brain tabotropic. Both play important roles in mediat- guanine to cytosine results in a change from arginine to ing excitotoxic and inflammatory cell damage (Friedlander proline (Ara et al. Caspases are cysteine-dependent proteases that play a cantly more effective at initiating apoptosis (Dumont et al. Poor outcome in this sample was as- microfilaments and microtubules (Friedlander 2003). Sur- sociated with a higher percentage of individuals homozy- prisingly, relatively little is known about functional poly- gous for the Arg allele. Thus, although caspase- Angiotensin Converting Enzyme and calpain-related genes may well be targets in the future, there are no known likely candidates at this time. Our group after mild brain injury and a novel cytosine to thyronine found an association between the presence of the G allele substitution resulting in a switch from serine (hydro- and reduced temporal lobe gray matter in elderly individ- philic) to leucine (hydrophobic) at codon 218. Interest- recently reported an additional two patients with this ingly, Winter et al. Cytokines there are likely to be others that are identified in the next are a diverse group of soluble proteins and peptides that several years. They are activated through interaction with the caspases and related pro- and Plasticity teases, thus it is important to consider the interaction of these two systems in considering response to trauma. An- Given equivalent amounts of primary and secondary in- imal models and some human data (Holmin et al. Generally it is now accepted that neurogenesis occurs in the adult human brain (Kaneko and Sawamoto 2009; Interleukin-1 Family Kempermann 2002a; Schaffer and Gage 2004). Functional polymorphisms exist within this fam- identified (for reviews, see Kaneko and Sawamoto 2009 ily. There are few reports of common functional poly- 40 Textbook of Traumatic Brain Injury morphic alleles identified in the genes coding for the com- 196 involving a change from G to A, with a subsequent ponent processes of neurogenesis, although this is likely change in amino acid from valine to methionine (Egan et to change in the future. There was a significant main ef- fect of genotype on Wechsler Memory Scale-Revised scores, with the Met/Met group scoring lower than the Val/ Serotonin Transporter Met or Val/Val groups. The role of Val66Met polymorphism in tonin from the synapse back into the presynaptic neuron. Repair Adaptive Synaptic Organization Apolipoprotein E The second major component in repair/regeneration/plas- ticity is synaptic organization. Neurotrophic factors play a Another candidate gene of interest in response and repair key role in this process. In brief, there are four broad cilitates the uptake, transport, and distribution of lipids. Neurotrophins play a role in the protection amino acids at positions 112 and 158: *E2 (cysteine/cys- and maintenance of neurons, neurogenesis, and synaptic teine), *E3 (cysteine/arginine), and *E4 (arginine/argin- plasticity (Mufson et al. ApoE appears to play an important role in neuronal families include factors that in theory could be relevant to repair and plasticity after neurotrauma (Chen et al. The Animal models suggest a link between the *E4 allele and best, albeit limited, evidence suggests roles for several increased mortality, extent of damage, and poor repair fol- members of the nerve growth factor family and the glial- lowing trauma (Chen et al. The derived factor family in the response to neurotrauma human *E4 allele has been associated with a variety of dis- (Hicks et al. In this study, worse outcome meant being in a trauma and remains elevated for several days (Hicks et al. Recently, Willemse-van There are also several polymorphisms in the promoter re- Son et al. In Alzheimer’s dis- ease, the degree of reduction of choline acetyl transferase, Pre- and Postinjury Cognitive one of the markers for the disease, is correlated with the “dose” of *E4 (Chen et al. A diated through reduced cholinergic input to posterior pa- large number of factors determine cognitive performance, rietal systems regulating selective attention. However, it may be the case vations of progressive dementia in boxers with repetitive that the effects of different “cognitive alleles” are additive brain injury (Martland 1928), neuropathological studies and that in combination they might have measurable ef- showed prominent neurofibrillary tangles and subse- fects on outcome. In addition, such “adverse alleles” quently amyloid plaques similar to those found in Alz- might not be noticeable until an individual’s cognitive re- heimer’s disease and other neurodegenerative disorders serve is depleted by an injury. Dopamine plays an important role in the regulation and Such differences have led investigators to question modulation of mood, cognition (particularly memory, at- whether genetic factors play a role. For example, Mayeux tention, and executive functions), reward functions, endo- et al. Thus dopaminergic Alzheimer’s disease, comparing them with a control group system genes are ideal candidates to probe for roles in neu- of 123 healthy older individuals. To date most of the attention has 42 Textbook of Traumatic Brain Injury focused on polymorphisms in genes coding for dopamine teins known as transporters and are taken back into the receptor subtypes, dopamine reuptake (the dopamine presynaptic neuron.
Nutritional agents: More and more evidence is • The most common general pattern is that of a marked accumulating that nutritional factors play an important increase in incidence of cancer with increase in age cheap 25mg clomid with amex pregnancy 8th week. As far back as 1933 purchase clomid online pills pregnancy 0-3 months, Ian This pattern is seen in general in case of carcinomas 356 Morrison Orr incriminated low dietary vitamin A intake of skin purchase clomid with paypal womens health exercise book, gastrointestinal tract and urinary tract, as well in the etiology of oral cancer. Khanolkar was able to as in case of some nonepithelial cell cancers such as chronic lymphatic leukemia and myelomastosis. The rate of increase with age is very rapid and are an exceptional community in the world where has been calculated to be proportional to the fourth, cancer incidence is more in females compared to males. As an example, if the Heredity: Familial heredity definitely predisposes to increase is proportional to the fifth power, then a certain types of cancer. It has been shown in general cancer having an incidence of 1 per million at age that as regards the common types of cancer, a sibling 20 years will have an incidence of 1024 per million of an affected patient has twice the risk of developing at 80 years of age. A peak is seen of the increased risk is mediated through sharing similar in early life while the incidence is almost nil in later environment and habits. For example, nephroblastoma and retino- genetic and hereditary determinants of carcinogenesis blastoma occur only in children, while teratomas and are as follows: seminomas of the testis have peak incidence at 20 • Persons with blood group A have 20 percent higher and 30 years respectively. Its incidence increases with age up to • Polyposis coli (which is associated with a high risk of menopause, followed by a steady decline thereafter. Cancer of thigh and abdomen slower than that mentioned in clause (a) above as in Kashmir (Kangri cancer) is associated with the custom applicable to carcinomas. The connective tissue of using Kangri, a pot containing burning coals, to obtain sarcomas belong to this category. The occurrence of oral cancer is associated Sex: Half a century ago, cancer all over the world was with the custom of chewing a mixture of slaked lime, betel more common in women than in men but this was nut and tobacco. The habit of smoking is well known to largely due to the high incidence of cervical cancer and lead to cancer of lung. If one overlooks childhood is responsible for the lower incidence of cancer the cancer of sex specific organs (genital organs, breast, of penis and cervix among the Jews and Muslims. In Britain, lip cancer is 14 times and on the other hand, is a disease of aged spinsters. Both physical and socioeconomic environments may Race: Racial differences in incidence of carcinoma have influence the occurrence of cancer. On the other hand, the risk atmosphere may raise the incidence of leukemia and of chronic lymphatic leukemia and myelomatosis is less 17 other cancers. In India, distinct may be partly responsible for increased lung cancer differences in pattern of cancer have been found incidence. Some cancers are more common in low income groups, such as the cancers Health promotion: This relates mainly to health edu- of esophagus, stomach, skin and cervix. People should be motivated of breast cancer is high and that of cervical cancer low to change lifestyle patterns which predispose to cancers. Specific protection: No specific protective measures Pathogenesis comparable to vaccines in case of communicable diseases are available for prevention of cancer. The pathogenesis of cancer is the result of interaction However, several specific measures can be taken to between various agent, host and environmental factors. The preclinical stage Agent factors: consists of a latent period of several years followed by • The use of known chemical carcinogens in industry a period of cancer in situ in which localized tissue should be modified or avoided if possible. Three clinical stages ingredients of modern cosmetics and several of cancer are: pesticides. Stage of metastasis when secondary spread has • Undue exposure to harmful radiations should be occurred to organs remote from the primary site. Terminal stage when the disease is incurable and the should be avoided or reduced. It is often accompanied • Diet should be nutritionally adequate and well by marked cachexia. Systematic reevaluation and classi- cervix based on available data at the registries in fication of precancerous lesions is helpful. Cervical Bangalore, Kerala and Chennai show that it varies carcinoma is amenable to diagnosis at the preinvasion between 34. Benign tumors of skin and other epi- poor socioeconomic status and incomplete treatment thelial tissues may be potentially precancerous. Circumcision may be considered a good custom from Cancer prevention ought to be undertaken as a public this point of view. Early and prolonged breastfeeding health program, especially in respect of those cancers should be encouraged since it partly prevents against that have high incidence and are preventable. More than 75 percent cancers are Environmental factors: Many agent factors and some preventable by specific measures, including early host factors listed above may be rightly regarded as treatment of precancerous conditions, and by removal environmental factors as well. If cancer in situ is removed at a radiation, ultraviolet light and heat form a part of the very early and asymptomatic stage, it may not recur. Industrial products, air and water Delays in diagnosis and treatment are attributable to pollutants, drugs, diet and food activities may be patients in 33 percent cases, doctors in 20 percent cases considered as part of chemical environment. The remaining 37 percent infections associated with cancer may be regarded as cases are attributed to vague clinical symptoms and to forming the biological environment. Within this broad scope of environmental factors, Doll and Peto have grouped them into 13 monitored. According to them 30 percent cancer screening for oral cancer by trained health workers and deaths are attributable to diet and tobacco each, thus referral services from trained physicians, in addition to accounting for almost two-thirds of all cancer deaths. The three-year (1995 to 1998) The next two factors in degree of importance are incidence rate of oral cancers was 20. The three-year fatality Out of the remaining 16 percent cancer deaths, one- rates were 56. Results show that (radiations, ultraviolet light, pollution, food additives, an intensive intervention program can drastically reduce industrial products) while the rest are due to the incidence and mortality from oral cancers. Early Diagnosis and Treatment This is particularly important in advanced stage of cancer All persons should be instructed to self-examine in patients diagnosed late. Pain can be controlled by themselves after the age of 30 and go to the specialist appropriate analgesic therapy in 90 percent patients. Provision of suitable drugs for cancer pain relief may necessitate amendments in national drug legislation. Physical aids may be necessary after • Persistent cough or hoarseness amputation, laryngectomy, colostomy or face deforming • Excessive or irregular menstrual blood loss surgery. The last may have to be performed for sarcoma • Blood loss from any natural orifice of the jaw and carcinoma of maxillary antrum. Psycho- • A swelling or sore that does not get better logically, the patient has to be prepared to accept willingly the change after operation. The finding of malignant cells in body in India is 1/5th of the world’s total cases with 1,00,000 secretions helps in preclinical or early diagnosis. Approximately, 85 percent of women • X-ray and ultrasound technique to diagnoses who die from cervical cancer belong to developing different cancers at different sites.
Hypergonadotropic hypogonadism usually results from impaired testosterone production buy cheap clomid breast cancer grade, which can be congenital or acquired cheap clomid online master card women's health center greenville nc. The most common disorder is Klinefelter syndrome purchase clomid australia menstruation odors as you get older, as discussed earlier (Clinical Focus 36. Unless given at supraphysiologic doses, exogenous testosterone cannot achieve the required local high concentration in the testis. One function of androgen-binding protein in the testis is to sequester testosterone, which significantly increases its local concentration. High androgens have an anabolic effect on muscle tissue, leading to increased muscle mass, strength, and performance, a desired result for bodybuilders and athletes. Androgen abuse has been associated with abnormally aggressive behavior and the potential for increased incidence of liver and brain tumors. Pseudohermaphroditism produces gonads of one sex and the genitalia of the other in the same person. The term male pseudohermaphrodite is used when a testis is present, and the term female pseudohermaphrodite is used when an ovary is present. The term hermaphrodite is reserved for the very rare cases in which both ovarian and testicular tissues are present. One of the most interesting causes of male reproductive abnormalities is the insensitivity of the end organ to androgens. The best characterized syndrome is testicular feminization, an X-linked recessive disorder caused by a defect in the testosterone receptor. They have abdominal testes that secrete testosterone but no other internal genitalia of either sex (see Chapter 38). They commonly have female external genitalia but with a short vagina ending in a blind pouch. Breast development is typical of a female (as a result of peripheral aromatization of testosterone), but axillary and pubic hair, which are androgen dependent, are scarce or absent. Testosterone levels are normal or elevated, estradiol levels are above the normal male range, and circulating gonadotropin levels are high. The inguinally located testes usually have to be removed because of an increased risk of cancer. After orchiectomy, patients are treated with estradiol to maintain a female phenotype. It is estimated that infertility affects one in every six couples who are trying to conceive, with about half of the cases resulting from the inability of the male to initiate pregnancy. Causes of male infertility include abnormal sperm production or function, impaired delivery of sperm, general health and lifestyle issues, and exposure to certain environmental factors. Of new concern are findings that a modern day environmental factor, the cell phone, commonly carried close to the testicles (i. As importantly noted by this research team, many men carry their cell phones in a trouser pocket (or clipped to a waist belt) exposing testes to high-power cell phone density. As the effects of frequency, distance of the phone from the source, and the duration of talk time on spermatozoa are not known, current investigations by these researchers are now employing a two-dimensional anatomical model of the tissue to extrapolate the effects seen in in vitro condition to real-life conditions. Sperm develop from spermatogonia through a series of developmental stages that include spermatocytes and spermatids. At the time of ejaculation, muscular contractions of the epididymis and vas deferens move sperm through the ejaculatory ducts into the prostatic urethra. The testicular hormones complete a negative feedback loop with the hypothalamic–pituitary axis. Androgens have several target organs and have roles in regulating the development of secondary sex characteristics, the libido, and sexual behavior. The prostate gland, seminal vesicles, and bulbourethral glands secrete the seminal fluids. On examination, he was eunuchoidal and hypogonadal, and olfactory function testing showed he was anosmic. His appearance was very different from his alleged identical twin who had undergone a normal puberty and had normal plasma testosterone and gonadotropin levels. It is often associated with anosmia or hyposmia and is transmitted as an autosomal dominant trait. Describe how luteinizing hormone and follicle-stimulating hormone, in coordination with ovarian theca and granulosa cells, regulate the secretion of follicular estradiol. Explain how positive feedback of follicular estradiol on the hypothalamic–pituitary axis induces luteinizing hormone and follicle-stimulating hormone surges and causes ovulation. Outline the sequence of distinct steps in follicular development including how appropriately timed luteinizing hormone and follicle-stimulating hormone surges, which induce inflammatory reactions in the graafian follicle, lead to follicular rupture and ovulation. Describe the changes in hypothalamic secretory function at the onset of puberty that increase luteinizing hormone and follicle-stimulating hormone secretion, enhance ovarian function, and lead to the first ovulation. Explain the mechanism that results in menopause and describe the medical complications of this state for older women. The fertility of a women is cyclic, with the release of a mature ovum approximately once per month. The cyclic changes in steroid hormone secretion from the ovary cause significant changes in the structure and function of the uterus, preparing it for the reception of a fertilized ovum. Hormonal events during the menstrual cycle are delicately synchronized; thus, stress and environmental, psychologic, and social factors can readily affect the menstrual cycle. Under normal conditions, these changes follow a 28-day cycle resulting from the interaction of hormones released by the anterior pituitary and ovary. The ovarian steroids have positive effects on the reproductive tract and secondary sex characteristics. The ovary also produces three polypeptide hormones that regulate anterior pituitary hormone release. The sex steroids in women, estrogen, progesterone, and androgen, are present in and removed from the plasma through the same mechanisms as other steroid hormones (see Chapter 33). Of the three estrogens, estradiol, estrone, and estriol, estradiol is the most abundant and is many times more potent than estrone and estriol. Circulating progesterone binds to the plasma protein corticosteroid-binding protein (transcortin) and also to albumin. Binding proteins prolong the lifetime of the sex steroids, which are eventually cleared from the circulation by the liver, undergoing conversion to glucuronides or sulfates, and then excreted in the urine. The morphology and function of these structures change in a cyclic manner under the influence of the reproductive hormones. The ovaries are in the pelvic portion of the abdominal cavity on both sides of the uterus and are anchored by ligaments (Fig. An adult ovary weighs 8 to 12 g and consists of an outer cortex and an inner medulla, without a sharp demarcation. The cortex contains oocytes enclosed in follicles of various sizes, corpora lutea, corpora albicantia, and stromal cells.