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As such levitra professional 20 mg otc, they face an increased multiple birth defects buy generic levitra professional 20 mg on-line, and abnormal physical develop- risk in future pregnancies together of having another ment of the brain 20mg levitra professional otc. Thus buy levitra professional 20 mg without prescription, it is not possible to perform direct genetic testing to Description determine carrier status discount levitra professional 20mg, confirm a clinical diagnosis, or In 1971, Dr. Each child had an unusually small Demographics head (microcephaly) and abnormalities of their arms, Adequate data are not available to provide a specific legs, skin, and external genitalia. The condition is daughters were each stillborn, while the affected son only very rare. Laxova described a of Neu-Laxova syndrome had been reported up to that different family whose children had birth defects similar point in medical literature. Taken Signs and symptoms together, these two families were considered evidence of a previously unrecognized genetic syndrome. The disor- Stillborn or newborn infants with NLS have a char- der was named Neu-Laxova syndrome in honor of these acteristic pattern of internal and external abnormalities. Not all affected infants will have all of the features listed Neu-Laxova syndrome (NLS) has since become below, and some anomalies are slightly more common known as a rare, lethal inherited condition characterized than others. Their heads are very small, and scaly skin, generalized swelling of body tissues (edema), their foreheads appear to slant backwards. The external features of the head and face are a Agenesis of the corpus callosum—Failure of the reflection of severe physical abnormalities of the brain. The corpus is not unusual for an infant with NLS to have an under- callosum is the band of nerve fibers located developed cerebellum or even lissencephaly, a more seri- between the two sides, or hemispheres, of the ous malformation characterized by a smooth brain brain. Normal development of the brain includes an Cataract—A clouding of the eye lens or its sur- intricate pattern of grooves, or gyri, on its outer surface. Surgery may be per- dation among survivors and an increased frequency of formed to remove the cataract. Other reported brain malformations include agenesis of the corpus cal- Cerebellum—A portion of the brain consisting of losum and Dandy-Walker malformation. The cerebellum is involved in control A variety of limb abnormalities have also been of skeletal muscles and plays an important role in described in NLS. Affected individuals often have short- the coordination of voluntary muscle movement. It ened arms and legs that are held out from the body in an interrelates with other areas of the brain to facili- unusual, fixed position. This positioning is often referred tate a variety of movements, including maintaining to as flexion contractures. The fingers and toes may proper posture and balance, walking, running, and appear underdeveloped (hypoplastic) and/or fused fine motor skills, such as writing, dressing, and together (syndactyly). Cleft lip—A separation of the upper lip that is pres- Other abnormalities more common to NLS include ent from birth but originates early in fetal develop- markedly limited physical growth. A cleft lip may appear on one side during pregnancy and, as such, is referred to as intrauter- (unilateral) or both sides (bilateral) and is occa- ine growth restriction (IUGR). Surgery is amount of fluid in the tissues of the body, is a hallmark needed to completely repair cleft lip. The edema may either be generalized and very severe throughout the body or limited only to the face or Cleft palate—A congenital malformation in which scalp. The skin is often extremely dry and scaly, a med- there is an abnormal opening in the roof of the ical condition called ichthyosis. The lungs are often mouth that allows the nasal passages and the hypoplastic (underdeveloped), even when delivery occurs mouth to be improperly connected. The external genitalia are often abnormal, but Dandy-Walker malformation—A complex struc- this is more obvious in males than in females since males tural abnormality of the brain frequently associ- typically have a small, underdeveloped penis. Abnormalities in other excessive volume of amniotic fluid (polyhydramnios) areas of the body may also be present. This is due to a combination of abnormal with Dandy-Walker malformation have varying fluid production and impaired fetal swallowing from the degrees of mental handicap or none at all. The placenta is Placenta—The organ responsible for oxygen and also usually abnormal in appearance and function. Diagnosis Stillbirth—The birth of a baby who has died some- time during the pregnancy or delivery. Many infants with NLS have been born into families with no previous history of the disorder and/or ones in which the parents are unrelated. Thus, an exact diagnosis of NLS during pregnancy may be very difficult, particu- and the eyes are prominent or bulging.

Effects of opioids Lüllmann buy levitra professional 20mg without a prescription, Color Atlas of Pharmacology © 2000 Thieme All rights reserved discount 20mg levitra professional mastercard. Likewise order 20mg levitra professional amex, garding efficacy and potential for de- bladder function is affected; specifically pendence probably reflect differing af- bladder emptying is impaired due to in- finity and intrinsic activity profiles for creased tone of the vesicular sphincter levitra professional 20mg with visa. A giv- Uses: The endogenous opioids en sustance does not necessarily behave (metenkephalin order levitra professional 20mg on line, leuenkephalin,! The abuse potential brain barrier, thus preventing access to is also determined by kinetic properties, their sites of action even after parenter- because development of dependence is al administration (A). With any of the high-effica- parenterally, as well as epidurally or cy opioid analgesics, overdosage is like- intrathecally in the spinal cord. The opi- ly to result in respiratory paralysis (im- oids heroin and fentanyl are highly lipo- paired sensitivity of medullary chemo- philic, allowing rapid entry into the receptors to CO2). Because of its high potency, fenta- sible extent of respiratory depression is nyl is suitable for transdermal delivery thought to be less in partial agonist/ (A). The user may also resort to vomiting, particularly after first-time ad- other more unusual routes: opium can ministration or in the ambulant patient. Like other opioids the emetic center then predominates, bearing a hydroxyl group, morphine is which overrides the stimulation of area conjugated to glucuronic acid and elim- postrema chemoreceptors. Glucuronidation of the Opioids elicit pupillary narrowing OH-group at position 6, unlike that at (miosis) by stimulating the parasympa- position 3, does not affect affinity. The thetic portion (Edinger-Westphal nu- extent to which the 6-glucuronide con- cleus) of the oculomotor nucleus. At any rate, the ac- tility and tonus of gastrointestinal tivity of this polar metabolite needs to smooth muscle; segmentation is en- be taken into account in renal insuffi- hanced, but propulsive peristalsis is in- ciency (lower dosage or longer dosing hibited. Gastric emptying is delayed (py- loric spasm) and drainage of bile and pancreatic juice is impeded, because the Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Opioids 213 Met-Enkephalin Morphine Fentanyl CH2 CH2 N CH3 Tyr Gly Gly Phe Met N N CH3 CH3 C CH2 N O HO O OH H3C C O O O C CH3 O O Heroin A. Bioavailability of opioids with different routes of administration Opioid Oral Nasal application mucosa, e. Metabolism of morphine Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. With repeated adminis- Opioids in chronic pain: In the tration of opioids, their CNS effects can management of chronic pain, opioid lose intensity (increased tolerance). In plasma concentration must be kept con- the course of therapy, progressively tinuously in the effective range, because larger doses are needed to achieve the a fall below the critical level would same degree of pain relief. Like other opioids (hydromor- Therefore, dietetic and pharmacological phone, meperidine, pentazocine, co- measures should be taken prophylacti- deine), morphine is rapidly eliminated, cally to prevent constipation, whenever limiting its duration of action to approx. The effects of opioids can be time, is a major inconvenience for abolished by the antagonists naloxone chronic pain patients. Raising the indi- or naltrexone (A),irrespective of the re- vidual dose would permit the dosing ceptor type involved. Given by itself, interval to be lengthened; however, it neither has any effect in normal sub- would also lead to transient peaks jects; however, in opioid-dependent above the therapeutically required plas- subjects, both precipitate acute with- ma level with the attending risk of un- drawal signs. Because of its rapid pre- wanted toxic effects and tolerance de- systemic elimination, naloxone is only velopment. Naltrexone clude the use of controlled-release is metabolically more stable and is giv- preparations of morphine, a fentanyl en orally. Naloxone is effective as anti- adhesive patch, or a longer-acting opi- dote in the treatment of opioid-induced oid such as l-methadone. Since it is more properties of the latter, however, neces- rapidly eliminated than most opioids, sitate adjustment of dosage in the repeated doses may be needed. Naltrex- course of treatment, because low dos- one may be used as an adjunct in with- age during the first days of treatment drawal therapy. When the oral route is unavailable Both are classified as “low-ceiling” opi- opioids may be administered by contin- oids (B), because neither is capable of uous infusion (pump) and when appro- eliciting the maximal analgesic effect priate under control by the patient – ad- obtained with morphine or meperidine. When constipation becomes intol- of a full agonist during changeover to erable morphin can be applied near the the latter. Intoxication with buprenor- spinal cord permitting strong analgesic phine cannot be reversed with antago- effect at much lower total dosage. Opioids 215 CH3 µ N # Morphine O CH3 HO OH µ N # CH3 Meperidine C O CH2 CH2 CH2 O N µ # N CH3 C CH2 Fentanyl H3C O H C C CH µ 3 CH2 # N Pentazocine CH3 CH2 CH3 N µ HO # H2C CH HO Nalbuphine CH2 N HO O OH µ HO 0,1 1 10 100 # Naloxone O Dose (mg) HO O A.

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Connect it to an intermittent suction device to prevent the stomach lining from obstructing the lumen buy levitra professional 20mg otc. Sometimes it is necessary to cut off the tip to allow for the aspiration of larger pills or tablets order 20 mg levitra professional otc. The size varies from 10 to 18 French (1 French unit = ¹ ₃ mm in diameter levitra professional 20 mg with visa, see page 241) buy cheap levitra professional 20 mg on line. Salem-sump:A double-lumen tube order levitra professional 20mg otc, with the smaller tube acting as an air intake vent so that continuous suction can be applied. This is the best tube for irrigation and lavage because it will not collapse on itself. If a Salem-sump tube stops work- ing even after it is repositioned, often a “shot” of air from a catheter-tipped syringe in the air vent will clear the tube. The bal- loon is partially filled with mercury (5–7 mL using a tangentially directed 21- gauge needle, then the air is aspirated), which allows it to gravitate into the small bowel with the aid of peristalsis. After the tube is in the stomach, inflate the balloon with 5–10 mL of air, inject 2–3 mL of mer- cury into the balloon, and then aspirate the air. Feeding Tubes Virtually any NG tube can be used as a feeding tube, but it is preferable to place a spe- cially designed nasoduodenal feeding tube. These are of smaller diameter (usually 8 French) and are more pliable and comfortable for the patient. Weighted tips tend to travel into the duodenum, which helps prevent regurgitation and aspiration. Most are supplied with stylets that facilitate positioning, especially if fluoroscopic guidance is needed. Always verify the position of the feeding tube with an x-ray prior to starting tube feeding. Commonly used tubes include the mercury-weighted varieties (Keogh tube, Duo-Tube, Dobbhoff, Entriflex), the tungsten-weighted (Vivonex tube), and the unweighted pediatric feeding tubes. Sengstaken–Blakemore tube:A triple-lumen tube used exclusively for the con- trol of bleeding esophageal varices by tamponade. One lumen is for gastric aspira- tion, one is for the gastric balloon, and the third is for the esophageal balloon. Other types of tubes used to control esophageal bleeding include the Linton and Minnesota tubes. Ewald tube:An orogastric tube used almost exclusively for gastric evacuation of blood or drug overdose. Dennis, Baker, Leonard tubes: These are used for intraoperative decompression of the bowel and are manually passed into the bowel at the time of laparotomy. Inform the patient of the nature of the procedure and encourage cooperation if the pa- tient is able. Maintain 13 gentle pressure that will allow the tube to pass into the nasopharynx. When the patient can feel the tube in the back of the throat, ask patient to swallow small amounts of water through a straw as you advance the tube 2–3 in. To be sure that the tube is in the stomach, aspirate gastric contents or blow air into the tube with a catheter-tipped syringe and listen over the stomach with your stethoscope for a “pop” or “gurgle. NG tubes are usually attached either to low wall suction (Salem-sump type tubes with a vent) or to intermittent suction (Levin type tubes). The latter allows the tube to fall away from the gastric wall between suction cycles. Feeding and pediatric feeding tubes in adults are more difficult to insert because they are more flexible. Feed- ing tubes are best placed into the duodenum or jejunum in order to decrease the risk of aspiration. Administering 10 mg of metoclopramide (Reglan) IV 10 min before inser- tion of the tube assists in placing the tube into the duodenum. As the tube is advanced, air can be injected to confirm progression of the tube to the right, toward the duodenum. If the sound of the air becomes fainter, the tube is probably curling in the stomach. Pass the tube until a slight resistance is felt, heralding the presence of the tip of the tube at the pylorus. Holding constant pressure and slowly injecting water through the tube is often rewarded with a “give,” which signifies passage through the pylorus.

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It is thought that the differences in ates the inflammatory response levitra professional 20mg on line, one of the primary male and female hormones may cause this disparity order levitra professional 20 mg overnight delivery. Histamines stimulate the In the United States order levitra professional 20mg mastercard, the mortality rate—number of dilation—widening—of the walls of blood vessels and deaths—attributed to asthma increased 56% from 1979 to make them more porous so that more blood fluid and pro- 1998 cheap 20mg levitra professional free shipping. This inflammation buy 20 mg levitra professional with mastercard, along with the con- In general, it is difficult to pinpoint the precise striction of the muscles in walls of the bronchial airways, causes of the dramatic increase in asthma cases in the narrows the air passages and makes breathing more diffi- United States. These changes are what is referred to as an asthma poor diagnosis and management of individual cases of attack. However, after many years of rapid increases in are responsible for making the bronchial passageways asthma cases, some of the most recent evidence suggests “over reactive” (increasing the tendency of constricting that the number of asthma cases may actually be declin- or narrowing) in asthmatic patients are quite distinct from ing slightly. Further studies will be needed to confirm this the genes that regulate the action of the immune system. According to Global Initiative for Asthma (GINA), a world-wide asthma research and education program, there are over 150 million asthmatic individuals worldwide. Some studies have revealed a 75% increase in asthma cases between 1980 and 1994 globally. It is interesting to note that the incidence of asthma (Custom Medical Stock Photo, Inc. While about 2% of children in China display symptoms of asthma, approxi- Other studies have documented higher rates of child- mately 30% of young people in Britain have indications hood asthma in some less advantaged, minority inner city of this disease. In Australia, the incidence of asthma is populations in the United States than in wealthier subur- very high in Caucasian children, but much lower in ban communities. Why such variations exist in the prevalence of Personalities with asthma asthma in different populations remains an unsolved mystery. Some scientists speculate that lifestyle factors, The symptoms of asthma have been observed and recorded in the medical literature since the time of such as a lack of physical activity, increased obesity, and Hippocrates, a famous doctor living in ancient Grecian more time spent indoors may contribute to higher rates times. The National Library of Medicine-Breath of Life of asthma in more highly developed countries. It is also Exhibit identifies many well known personalities who possible that environmental irritants such as poor indoor had a medical history of asthma. Despite their illness, and outdoor air quality, along with the presence of they pursued their chosen professions with great vigor potent irritants such as cockroach allergens, may con- and energy. The prolific American musician, Leonard tribute to higher rates of childhood asthma in poorer Bernstein, who composed West Side Story as well as communities. Other factors that may prompt the onset of many other celebrated scores, struggled with asthma asthma are viral respiratory infections, low birth weight, throughout his life. Another classical composer from a and smaller than average air passageways in asthmatic much earlier era, Ludwig von Beethoven, wrote some of patients. Robert Joffrey, founder of the avant-garde Many studies have shown that children who are exposed Joffrey Ballet, pursued an active dancing career in spite to viruses that cause the common cold and other respira- of his asthma. Contemporary individuals with asthma include the folk singer Judy Collins, track and field tory infections at a very young age are less likely to champion Jackie Joyner-Kersee, and professional basket- develop asthma than their peers living in a more ball star Dennis Rodman. So children living at home with older siblings and those who spend part of their week in John Kennedy, 35th president of the United States, daycare centers may be less likely to develop asthma than developed asthma from allergies to dogs, horses, and children who do not interact with others of their own age other animals. Asthma patients are encouraged to learn to the occurrence of symptoms (such as seasonal varia- recognize their own special pattern of early warning tions), when asthma symptoms first appeared, any con- signs that signal the start of an asthma episode. Asthma nection between symptoms and exposure to possible symptoms can be quite variable and are usually allergens, any disturbances in sleep patterns, and the reversible. Classification is include x rays to eliminate other possible causes of air- based on the severity and frequency at which symptoms way obstruction (blockage) and allergy tests. Asthmatic patients are also Moderate asthma more likely to develop other respiratory diseases such as pneumonia. Symptoms may persist for Asthma triggers many days and may interfere with normal physical activity. Many indoor and outdoor factors can Severe asthma trigger or initiate typical symptoms of asthma, including Patients with severe asthma have ongoing, persistent allergies, viral respiratory infections, weather changes, symptoms of this disease. Medications containing aspirin also act as much more serious, and can be life threatening.

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This occurs order levitra professional 20mg otc, for example best 20 mg levitra professional, at 20Hz tions buy levitra professional 20mg with visa,musclelengthandforcebothvarysimul- in slow-twitch muscles and at 60–100 Hz in taneously cheap levitra professional 20mg without a prescription. The muscle tionthatbuildsonanisometriconeiscalledan force during tetanus can be as much as four afterloaded contraction purchase 20 mg levitra professional otc. A resting muscle con- Ca2+ concentration, which decreases to some taining ATP can be stretched like a rubber extent between superpositioned stimuli, re- band. Contracture is not caused by ac- stretch, which keeps the sliding filaments in tion potentials, but by persistent local depolari- the sarcomeres from separating, is influenced zation due, for example, to increased extra- to a small extent by the fascia (fibrous tissue). Muscle strength at increasing and decreasing stimulus frequencies Stimulus Range of summation Single contractions Tetanus 0 2 4 6 8 10 Time (s) B. Types of contractions Isometric Isotonic Resting tension curve 0 0 Length Isotonic, then Auxotonic After- isometric loaded Rest Isometric Rest Isotonic contraction contraction C. Isometric muscle force relative to sarcomere length 100 80 Skeletal muscle 60 Cardiac 40 muscle 20 0 1. Ibandregionareflexibleandfunctionas“elas- force of cardiac muscle at rest is greater than ticbands”thatcounteractpassivestretchingof that of skeletal muscle (! Skeletal muscle normally functions in the plateau region of its length–force curve, The extensibility of titin molecules, which can stretchtouptoaroundtentimestheirnormallength whereascardiacmuscletendstooperateinthe in skeletal muscle and somewhat less in cardiac ascendinglimb(belowLmax)ofitslength–force muscle, is mainly due to frequent repetition of the curve without a plateau (! In very the ventricle responds to increased diastolic strong muscle extension, which represents the filling loads by increasing its force develop- steepestpartoftherestingextensibilitycurve(! Action potentials in cardiac muscle are of The length (L) and force (F) or “tension” of a much longer duration than those in skeletal muscle are closely related (! Since the active force is deter- allows the slow influx of Ca2+, causing the ac- mined by the magnitude of all potential actin- tionpotentialtoreachaplateau. Asaresult,the myosin interactions, it varies in accordance refractory period does not end until a contrac- with the initial sarcomere length (! There- Skeletal muscle can develop maximum active fore, tetanus cannot be evoked in cardiac (isometric) force (F )0 from its resting length muscle. Instead, the stimulus spreads of the thin filaments overlap, allowing only across all myocardial fibers of the atria and forces smaller than F0 to develop (! When subsequently of the ventricles generating an L is 70% of Lmax (sarcomere length: 1. In addition, Incardiacmusclebutnotinskeletalmuscle, a greatly pre-extended muscle (L " Lmax) can the duration of an action potential can change develop only restricted force, because the the force of contraction, which is controlled by number of potentially available actin–myosin the variable influx of Ca2+ into the cell. When extended to The greater the force (load), the lower the 130%ormoreoftheLmax,theextensionforceat velocity of an (isotonic) contraction (see velo- rest becomes a major part of the total muscle city–force diagram, F1). Light loads can muscle length, and ventricular pressure corre- therefore be picked up more quickly than sponds to muscle force;! Thetotalamountofenergy the cytosolic Ca2+ concentration can modify consumed for work and heat is greater in thepressure–volumerelationshipbycausinga isotonic contractions than in isometric ones. Muscle power is the product of force and the Other important functional differences be- shortening velocity: N·m·s–1 = W (! Active and passive components of muscle force (skeletal muscle) 100 Active muscle force Passive resting tension force Relative 0 muscle length 80 90 100 (length at max. Length-force curve for skeletal and cardiac muscle 1 Striated muscle 2 Cardiac muscle Total force Total force 200 200 Active Resting force tension force 100 100 Active Resting force tension force 0 0 65 100 135 80 100 120 Relative muscle length Relative muscle length (length at max. Muscle force (or load) and shortening velocity Maximum velocity (V ) 1 100 max 2 light Power with Fast Load small load Slow large load heavy Time 0 Load = muscle force 69 Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. The second type, multi-unit Smooth muscle (SmM) consists of multiple SmM, contracts primarily due to stimuli from layers of spindle-shaped cells. It is involved in the autonomic nervous system (neurogenic the function of many organs (stomach, in- tonus). This occurs in structures such as the testine, gall bladder, urinary bladder, uterus, arterioles, spermatic ducts, iris, ciliary body, bronchi, eyes, etc. Since where it plays an important role in circulatory these SmM cells generally are not connected control. SmM contains a special type of F- by gap junctions, stimulation remains local- actin-tropomyosin and myosin II filaments ized, as in the motor units of the skeletal (! Furthermore, it has no distinct tubular system Smooth muscle tonus is regulated by the and no sarcomeres (nonstriated). An in- which also provide a mechanical means for creaseintonuswilloccurifanyofthesefactors cell–cell binding of SmM.

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