Gary S. Wasserman, DO

• Chief, Section of Medical Toxicology
• Professor of Pediatrics
• University of Missouri?ansas City
• Children? Mercy Hospitals & Clinics
• Kansas City, Missouri

Recurrent attacks may occur antibiotic resistance coalition buy clindamycin in united states online, usually during periods when the person is feeling run down infection precautions purchase 300 mg clindamycin free shipping, anxious virus rash cheap clindamycin online visa, or depressed virus kingdom buy generic clindamycin online, before menstruation antimicrobial light purchase clindamycin cheap online, or after sexual intercourse infection under crown generic clindamycin 150mg line. The virus can be spread to others through sexual intercourse even when symptoms are absent. Genital herpes may be passed from a pregnant woman to her baby during 281 delivery. If the virus can be detected in vaginal swabs, delivery by caesarean section is usually recommended. Severe herpes gestationis is treated with corticosteroid drugs in tablet form and may require hospital admission. The disorder usually clears up completely after birth of the baby, but tends to recur in subsequent pregnancies. The initial infection may be symptomless, or may cause a flu-like illness with mouth ulcers. Rarely, the virus infects the fingers, causing a painful eruption called a herpetic whitlow. The virus may cause a potentially fatal generalized infection in a person with an immunodeficiency disorder or in someone taking immunosuppressant drugs. Antiviral drugs, such as aciclovir, may be helpful, particularly if used early in an infection. After an attack of chickenpox, some of the viruses survive and lie dormant for many years. In some people, a decline in the efficiency of the immune system, especially in old age or because of disease, allows the viruses to re-emerge and cause herpes zoster. Herpes zoster is also common in people whose immune system is weakened by stress or by certain drugs, such as corticosteroid drugs or anticancer drugs. The first indication of herpes zoster is excessive sensitivity in the skin, followed by pain. After about 5 days, the rash appears as small, raised, red spots that soon turn into blisters. The most serious feature of herpes zoster is pain after the attack (postherpetic pain), caused by nerve damage, which may last for months or years. If treatment is begun soon after the rash appears, antiviral drugs, such as aciclovir, will reduce the severity of the symptoms and minimize nerve damage. The cause is unknown but it is more common in obese people and those with a long-term cough, such as smokers. Before the vaccine was generally available, Hib infection was a common cause of bacterial meningitis and epiglottitis in children. Most attacks of hiccups last only a few minutes, and are not medically significant. Rarely, they may be due to a condition, such as pneumonia or pancreatitis, that causes irritation of the diaphragm or phrenic nerves. Chlorpromazine, haloperidol, or diazepam may be prescribed for frequent, prolonged attacks. Hickman catheter A flexible plastic tube, also known as a skin-tunnelled catheter, that is passed through the chest and inserted into the subclavian vein, which leads to the heart. It is often used in people who have leukaemia or other cancers and need regular chemotherapy and blood tests. The catheter allows drugs to be injected directly into the bloodstream and blood samples to be obtained easily. It can remain in position for months; the external end is plugged when not in use. Abscesses develop beneath the skin, which becomes reddened and painful and may ooze pus. The condition tends to be recurrent and can eventually cause scarring in the affected areas. Tough ligaments attach the femur to the pelvis, further stabilizing the joint and providing it with the necessary strength to support the weight of the body and take the strain of leg movements. Clicking hip is caused by a tendon slipping over the bony prominence on the outside of the femur, and does not indicate disease. Clicking of the hip that can be heard during examination of newborn babies indicates possible dislocation of the hip (see developmenal hip displasia). The hippocampus, consisting of a band of grey matter, is involved with some learning processes and long-term memory storage. It may also be needed if rheumatoid arthritis has spread to the hip joint or if the top end of the femur is badly fractured (see femur, fracture of). Symptoms, which include constipation and bloating, usually develop in the first few weeks of life, but may become evident in infancy or early childhood. The additional hair is coarse and grows in a male pattern on the face, trunk, and limbs. Hirsutism is a symptom of certain conditions, such as polycystic ovary syndrome (see ovary, polycystic) and congenital adrenal hyperplasia, in which the level of male hormones in the blood is abnormally high. Hirsutism can also be a result of taking anabolic steroids (see steroids, anabolic). More commonly, however, hirsutism is not a sign of any disorder; it occurs in many normal women, especially after the menopause. H1 activation is responsible for the swelling and redness that occur in inflammation. The cause is unknown, but histiocytosis X probably results from a disturbance of the immune system. In the mildest form, rapid cell growth occurs in 1 bone only, usually the skull, a clavicle, a rib, or a vertebra, causing swelling and pain. In the most severe, and least common, form, there is a rash and enlargement of the liver, spleen, and lymph nodes. Certain types of histocompatibility antigens are essential for the immunological function of killer T cells (see lymphocytes). The antigens act as a guide for killer T cells to recognize and kill abnormal or foreign cells. Short-lived hoarseness is often due to overuse of the voice, which strains the muscles in the larynx. It is also commonly caused by inflammation of the vocal cords in acute laryngitis. In people with hypothyroidism, hoarseness can result from formation of tissue on the vocal cords. Occasionally persistent hoarseness in adults has a more serious cause, such as cancer of the larynx (see larynx, cancer of), thyroid cancer, or lung cancer. The most common sign is the painless enlargement of lymph nodes, typically in the neck or armpits. There may be a general feeling of illness, with fever, weight loss, and night sweats. As the disease progresses, the immune system becomes increasingly impaired and lifethreatening complications may result from normally trivial infections. If the disease has spread to involve many organs, long-term treatment with anticancer drugs is needed. A holistic approach is emphasized by many practitioners of complementary medicine. The monitor records by means of electrodes attached to the chest and allows the detection of intermittent arrhythmias. Homeopathy involves administering minute doses of medicines which, in a healthy person, would be capable of inducing symptoms of the condition that is being treated. Homeostasis regulates conditions such as temperature and acidity by negative feedback. For example, when the body overheats, sweating is stimulated until the temperature returns to normal. Homeostasis also involves the regulation of blood pressure and blood glucose levels. Homocystinuria is a type of inborn error of metabolism (see metabolism, inborn errors of) in which there is an abnormal presence of homocystine (an amino acid) in the blood and urine. In heavier infestations, migration of the larvae through the lungs may produce cough and pneumonia; adult worms in the intestines may cause abdominal discomfort. Hormones are also secreted by other organs, including the brain, kidneys, intestines, and, in pregnant women, the placenta. The hormones may be taken orally or released into the bloodstream from a hormonal implant, skin patch, or gel. In some women, oestrogen therapy may increase the risk of abnormal blood clotting. The joined kidneys usually function normally, but may be associated with other congenital kidney defects. Hot flushes are usually caused by decreased oestrogen production during or after the menopause, and they sometimes occur following removal of the ovaries (see oophorectomy). The inflammation is usually caused by prolonged kneeling but may develop after a blow to the front of the knee. Infection with some of these strains is thought to be a causative factor in cervical cancer and anal cancer. The dome-shaped head of the bone lies at an angle to the shaft and fits into a socket in the scapula to form the shoulder joint. It flattens and widens at its lower end, forming a prominence on each side called an epicondyle. The term humours usually refers to the aqueous humour and vitreous humour that occur in the eye. Hunger occurs when the stomach is empty and the blood glucose level is low, often following strenuous exercise. In response to these stimuli, messages from the hypothalamus cause the muscular stomach wall to contract in a rhythmic manner; these contractions, if they are pronounced, produce hunger pains. Hunger due to a low blood sugar level can also occur in thyrotoxicosis, and in diabetes mellitus when an incorrect balance between insulin and carbohydrate intake causes hypoglycaemia. The disease is due to a defective gene and is inherited in an autosomal dominant manner (see genetic disorders). The chorea usually affects the face, arms, and trunk, resulting in random grimaces and twitches, and clumsiness. Dementia takes the form of irritability, personality and behavioural changes, memory loss, and apathy. If the condition is diagnosed in early infancy, a bone marrow transplant may be curative. Larvae mostly settle in the liver, lungs, or muscle, causing the development of cysts. The infestation is generally confined to dogs and sheep, but may be passed on to humans through accidental ingestion of worm eggs from materials contaminated with dog faeces. Cysts in the liver may cause a tender lump or lead to bile duct obstruction and jaundice. Cysts in the lungs may press on an airway and cause inflammation; rupture of a lung cyst may cause chest pain, the coughing up of blood, and wheezing. The mole, which resembles a bunch of grapes, is caused by degeneration of the chorionic villi. In a small number of affected pregnancies, the mole develops into a choriocarcinoma. Urine and blood tests detect excessive amounts of human chorionic gonadotrophin (see gonadotrophin, human chorionic), which 288 is produced by the tumour. The tumour can be removed by suction, a D and C, or, less commonly, a hysterectomy. Hydralazine may cause nausea, headache, dizziness, irregular heartbeat, loss of appetite, rash, and joint pain. A hydrocele may be caused by inflammation, infection, or injury to the testis; occasionally, the cause is a tumour. If the swelling is uncomfortable or painful, however, the fluid may be withdrawn through a needle. The condition may be present at birth, when it is often associated with other abnormalities, such as spina bifida, or it may develop as a result of major head injury, brain haemorrhage, infection (such as meningitis), or a tumour. With congenital hydrocephalus, the main feature is an enlarged head that continues to grow rapidly. If it is not treated, hydrocephalus progresses to severe brain damage, which may result in death within weeks. When the condition occurs later in life, symptoms include headache, vomiting, loss of coordination, and the deterioration of mental function. In most cases, treatment of hydrocephalus is by draining the fluid from the brain to another part of the body, such as the abdominal cavity, where it can be absorbed. Synthetic hydrocortisone is used as a corticosteroid drug to treat inflammatory or allergic conditions, such as ulcerative colitis or dermatitis. The obstruction of a ureter may be caused by a stone (see calculus, urinary tract), a kidney tumour, or a blood clot. Occasionally, hydronephrosis is caused by obstruction to the outflow of urine from the bladder by an enlarged prostate gland (see prostate, enlarged). Acute hydronephrosis, with sudden blockage of the ureter, causes severe pain in the loin. Chronic hydronephrosis, in which the obstruction develops slowly, may cause no symptoms until total blockage results in kidney failure.

Heavy irradiation has been shown to induce nondisjunction in some experimental animals antibiotic 294 purchase clindamycin with a mastercard, but there is no good evidence for a detectable effect on human trisomy (choice E) infection 8 weeks postpartum generic clindamycin 150 mg line. The presence of an expanded trinucleotide repeat in the 5 untranslated region of the gene is an accurate test for fragile X syndrome antimicrobial underlayment discount clindamycin 300mg with mastercard. However bacteria have dna order clindamycin 150mg line, many other syndromes also include mental retardation as a feature antibiotic resistance and farm animals order clindamycin 300 mg with mastercard, so this would not be a specific test antibiotic natural alternatives generic 300 mg clindamycin overnight delivery. Testicular volume (choice E) is increased in males with fragile X syndrome, but this is observed in postpubertal males. Fetal tissue the fetus has 46 chromosomes, indicating euploidy (a multiple of 23), not aneuploidy (choice A). Nondisjunction during meiosis (choice C) produces full trisomies and chromosomes have normal structure. Although the father is a translocation carrier, his genetic material is balanced, not unbalanced (choice E). It should be high on the differential diagnosis list for a female adolescent of short stature who presents with primary amenorrhea. Women with Turner syndrome have streak gonads, and the absence of ovarian function is responsible for failure to develop many secondary sex characteristics. Balanced translocations (choices B and C) have few, if any, consequences on the phenotype, although they may result in pregnancy loss of conceptions with unbalanced chromosome material. Deletion of a locus subject to imprinting (choice E) is consistent with Prader-Will syndrome or Angelman syndrome but is not associated with the phenotype described. The fetus has unbalanced chromosomal material (additional chromosomal material on one copy of chromosome 18). One of the parents is likely to be a carrier of a reciprocal translocation involving chromosome 18 and one other chromosome (unspecified in stem). A Robertsonian translocation (choice B) would result in fusion of q arms from two acrocentric chromosomes. Isochromosome 18(p) indicates a chromosome 18 with two p arms and no q arms (choice C). Nondisjunction during either meiosis 1 or meiosis 2 (choices D and E) would produce a full trisomy. Chromosomal abnormalities are responsible for about 50% of first trimester spontaneous abortions, and of these the most common cause is trisomy (52%). All other listed causes can also cause miscarriage; however, these problems are less common than chromosomal anomalies. These diseases tend to cluster in families (familial), but they do not conform to mendelian pedigree patterns. This chapter reviews some basic principles of the genetics of common, complex diseases. Because several genes and influential environmental factors contribute to the liability, its distribution in the population can be represented as a Gaussian ("bell-shaped") curve. Population (B) Threshold of and Prevalence of Obesity (B) Threshold for and Prevalence of Obesity Multifactorial Threshold Model Unlike liability for a disease, the multifactorial diseases themselves are not continuous traits. Expression of the disease phenotype occurs only when a certain threshold of liability is reached. As a simple example, obesity is a complex, multifactorial condition in which excess body fat may put a person at risk for a variety of other conditions, including type 2 diabetes and cardiovascular disease (see below). Threshold Number of Individuals Low Liability High Number of Individuals Threshold Low Liability High the male threshold is lower than the female threshold, so the prevalence of the disease is higher in males than in females. In contrast, the genes and environmental factors underlying multifactorial traits have not been identified specifically. For example, if we wish to know the recurrence risk for siblings of individuals with cleft lip and/or palate, we ascertain a large cohort of individuals with cleft lip and/or palate and then measure the proportion of their siblings who are also affected with cleft lip and/or palate (in this case, the sibling recurrence risk is approximately 3%, which is considerably higher than the general population prevalence of 0. This does not mean that the true risk has changed; rather, it reflects the fact that additional affected individuals provide more information about the true risk. The presence of multiple affected individuals indicates that the family is located higher on the liability distribution. For example, one study showed that sibling recurrence risk for a neural tube defect (spina bifida or anencephaly; see Clinical Correlate) was 3% if one sibling was affected, 12% if two were affected, and 25% if 3 were affected. For example, the prevalence of pyloric stenosis (congenital constriction of the pylorus) is approximately 1/1,000 for females and 1/200 for males. Thus, the average affected female is likely to be located higher on the liability distribution than is an affected male. For example, 374 Chapter 4 Genetics of Common Diseases successive degree of relationship. Although the recurrence risk for a single-gene disorder remains the same regardless of the prevalence of the disease in a population, the empirical risk for multifactorial diseases increases as the population prevalence increases. This is because populations with higher prevalence rates have a higher preponderance of genetic and environmental risk factors. Anencephaly (partial or complete absence of the brain) usually leads to a stillbirth, and anencephalics that survive to term do not live for more than a few days. Spina bifida, a protrusion of spinal tissue through the vertebral column, produces secondary hydrocephalus in 75% of cases and often produces some degree of paralysis. Improved intervention strategies have increased survival rates substantially for this condition, with more than two thirds of patients now surviving beyond 10 years of age. Folic acid deficiency is likely to be present in successive pregnancies, providing a nongenetic explanation for some of the familial clustering of this disease. However, there is also evidence for genetic variation in the ability to metabolize folic acid. The fraction (or percent) of the population above the threshold defines the prevalence of the disease in that population. Recurrence risks increase with the number of affected relatives, the severity of disease expression in the family, the probands of the less commonly affected sex, and the prevalence of disease in the population. Pyloric stenosis is 5 times more common in males than in females in certain Japanese populations. The liability curve for the development of this condition in that population is shown below: Number of individuals Liability Male threshold Female threshold Within this population, which of the following is most at risk for the development of disease Because the trait in this case is 5 times more common in males in females, it means that males are found lower on the liability curve. Therefore, a female with the disease is higher on the liability curve and has a larger number of factors promoting disease. The highest risk population in this model of multifactorial inheritance would be the sons (the higher risk group) of affected mothers (the lower risk group). The affected mother had an accumulation of more disease-promoting liabilities, so she is likely to transmit these to her sons, who need fewer liabilities to develop the syndrome. This chapter provides an overview of the techniques that have been used to map and clone thousands of human genes. There are several classes of polymorphic markers; over 20,000 individual examples of these polymorphic markers at known locations have been identified and are available for linkage studies. A specific site may be present in some individuals (allele 1) and absent in others (allele 2), producing different-sized restriction fragments that can be visualized on a Southern blot. The repeat is flanked on both sides by a restriction site, and variation in the number of repeats produces restriction fragments of varying size. These markers have many alleles in the population, with each different repeat length at a locus representing a different allele. This can be done by recombination mapping to determine whether the gene is near a particular marker. Multiple markers on different chromosomes are used to establish linkage (or the lack of it). Recombination mapping is based on crossing over during meiosis, the type of cell division that produces haploid ova and sperm. The Process of Crossing Over Between Homologous Chromosomes When a crossover event occurs between two loci, G and M, the resulting chromosomes may contain a new combination of alleles at loci G and M. Because crossover events occur more or less randomly across chromosomes, loci that are located farther apart are more likely to experience an intervening crossover and thus a recombination of alleles. Recombination frequency provides a means of assessing the distance between loci on chromosomes, a key goal of gene mapping. The larger distance between the gene and the marker allows multiple crossovers to occur between the alleles during prophase I of meiosis. An odd number of crossovers separates G1 from M1 (recombination), whereas an even number of crossovers places the alleles together on the same chromosome (no recombination). Therefore, G1 and M1 are likely to remain on the same chromosome more than 50% of the time. If a cell gets G1, then 50% of the time it will get M1 and 50% of the time it will get M2. If cell gets G1, then 50% of the time it will get M1 (even number of crossovers) and 50% of the time it will get M2 (odd number of crossovers). M1 M2 No recombination G1 M2 B G2 M1 Recombination Gene and marker are close together on the same chromosome. Therefore, recombination frequency can be used to estimate proximity between a gene and a linked marker. Some members of the family have the disease-producing allele of the gene (indicated by phenotype in the pedigree) whose location is to be determined. Three steps are involved in determining whether linkage exists and, if so, estimating the distance between the gene and the known marker. Establish linkage phase between the disease-producing allele of the gene and an allele of the marker in the family. A family in which a mutation causing neurofibromatosis type 1 is transmitted in 3 generations. Is it also possible to determine which allele of the marker was passed from the grandmother to her daughter If linkage is present, the diseaseproducing allele (A) is linked to allele 1 of the marker. Recombination frequencies can be related to physical distance by the centimorgan (cM) the recombination frequency provides a measure of genetic distance between any pair of linked loci. For example, if two loci show a recombination frequency of 2%, they are said to be 2 centimorgans apart. This relationship is only approximate, however, because crossover frequencies are somewhat different throughout the genome. In fact, there is some small chance that the gene and the marker are not actually linked at all and the data were obtained by chance. We could be more confident that our conclusions were correct if we had used a much larger population. The "odds of linkage" is simply the probability that each recombination frequency () is consistent with the family data. If data from multiple families are combined, the numbers can be added by using the log10 of these odds. Therefore, the most likely distance between the gene and the marker is a recombination frequency of 10%, or 10 cM. In practice, markers that are useful for genetic testing must show less than 1% recombination with the gene involved (be <1 cM distant from the gene). A family with an autosomal dominant disorder is typed for a 2 allele marker, which is closely linked to the disease locus. A man who has alkaptonuria marries a woman who has hereditary sucrose intolerance. Both are autosomal recessive diseases and both map to 3q with a distance of 10 cM separating the two loci. What is the chance they will have a child with alkaptonuria and sucrose intolerance In a family study following an autosomal dominant trait through 3 generations, two loci are compared for their potential linkage to the disease locus. In this pedigree, the disease allele is consistently transmitted with the 1 allele. There is no case in this small number of individuals where recombination between these two loci has occurred. Linked markers can be "uninformative" (choice E) in some pedigrees if, for example, the same alleles are expressed in all family members. A child will inherit a gene for alkaptonuria from the father and the normal allele of this gene from the mother. Conversely, the child will inherit a gene for hereditary sucrose intolerance from the mother and a normal allele of this gene from the father. The child will therefore be a carrier for each disease but will not be affected with either one. In each case, individuals who receive the A allele also receive the disease allele. The goal of genetic diagnosis is to determine whether an at-risk individual has inherited a disease-causing gene. Note that this test merely determines genotype, and many considerations must be taken into account before predictions about phenotype could be made. Hemochromatosis has only about 15% penetrance, and in those who do have symptoms, variable expression is seen. This approach has the advantages of ready computerization and miniaturization (hundreds of thousands of oligonucleotides can be embedded on a single 2-cm2 chip). This disease shows anticipation, and family members with a severe form of myotonic dystrophy may have several thousand copies of this repeat.

Inguinal Hernias Herniation of abdominal viscera can occur in one of several weak aspects of the abdominal wall antimicrobial vinegar order clindamycin. Inguinal hernias are the most common of the abdominal hernias and occur more frequently in males due to the inherent weakness of the male inguinal canal antibiotics for uti augmentin purchase clindamycin without prescription. After passing through the inguinal canal and superficial ring antimicrobial qualities order 150mg clindamycin, the viscera can continue and coil in the scrotum antimicrobial drugs quizlet best purchase clindamycin. Note Direct hernias are found medial to the inferior epigastric vessels antibiotic vitamins clindamycin 150 mg, and indirect inguinal hernias occur lateral to the inferior epigastric vessels antimicrobial 24-7 order on line clindamycin. While the epithelial lining of the mucosa of the primitive gut tube is derived from endoderm, the lamina propria, muscularis mucosae, submucosa, muscularis externa, and adventitia/serosa are derived from mesoderm. The primitive gut tube is divided into the foregut, midgut, and hindgut, each supplied by a specific artery and autonomic nerves. Note that the liver develops in the ventral embryonic mesentery, and the spleen and dorsal pancreatic bud develop in the dorsal embryonic mesentery. The original left side of the stomach before rotation becomes the ventral surface after rotation and its anterior and posterior borders before rotation will become the lesser and greater curvatures, respectively. Dorsal Microbiology Clinical Correlate Inflammation of the parietal peritoneum (peritonitis) results in sharp pain that is localized over the area. Peritoneum the parietal layer lines the body wall and covers the retroperitoneal organs on one surface. Parietal peritoneum is very sensitive to somatic pain and is innervated by the lower intercostal nerves and the ilioinguinal and the iliohypogastric nerves of the lumbar plexus. The only communication between the lesser sac and the greater sac is the epiploic foramen (of Winslow). Intraperitoneal versus Retroperitoneal Organs the abdominal viscera are classified according to their relationship to the peritoneum. Many retroperitoneal organs are originally suspended by a mesentery and become secondarily retroperitoneal. In secondary retroperitonealization, parts of the gut tube (most of the duodenum, pancreas, ascending colon, descending colon, part of rectum) fuse with the body wall by way of fusion of visceral peritoneum with parietal peritoneum. This causes the organs to become secondarily retroperitoneal (and the visceral peritoneum covering the organ is renamed as the parietal peritoneum). The vessels within the mesentery of these gut structures become secondarily retroperitoneal. The embryonic mesentery between the spleen and the gut tube becomes the gastrosplenic ligament. The mesentery between the spleen and the dorsal body wall becomes the splenorenal ligament. It is associated with polyhydramnios; projectile, nonbilious vomiting; and a small knot at the right costal margin. Extrahepatic biliary atresia occurs when the lumen of the biliary ducts is occluded owing to incomplete recanalization. Annular pancreas occurs when the ventral and dorsal pancreatic buds form a ring around the duodenum, thereby causing an obstruction of the duodenum and polyhydramnios. It is associated with polyhydramnios, bile-containing vomitus, and a distended stomach. An omphalocele occurs when the midgut loop fails to return to the abdominal cavity and remains in the umbilical stalk. The viscera herniate through the umbilical ring and are contained in a shiny sac of amnion at the base of the umbilical cord. It is often associated with multiple anomalies of the heart and nervous system, with a high mortality rate (25%). Gastroschisis occurs when the abdominal viscera herniate through the body wall directly into the amniotic cavity, usually to the right of the umbilicus. Ileal (Meckel) diverticulum occurs when a remnant of the vitelline duct persists, thereby forming a blind pouch on the antimesenteric border of the ileum. It is often asymptomatic but can become inflamed if it contains ectopic gastric, pancreatic, or endometrial tissue, which may produce ulceration. It is typically found 2 feet from the ileocecal junction, are 2 inches long, and appears in 2% of the population. Vitelline fistula occurs when the vitelline duct persists, thereby forming a direct connection between the intestinal lumen and the outside of the body at the umbilicus. Malrotation of midgut occurs when the midgut undergoes only partial rotation and results in abnormal position of abdominal viscera. Colonic aganglionosis (Hirschsprung disease) results from the failure of neural crest cells to form the myenteric plexus in the sigmoid colon and rectum. It is associated with loss of peristalsis and immobility of the hindgut, fecal retention and abdominal distention of the transverse colon (megacolon). It lies mostly in the right aspect of the abdominal cavity and is protected by the rib cage. They receive their blood supply from the left branches of the portal vein and hepatic artery and secrete bile to the left hepatic duct. The hepatic veins drain the liver by collecting blood from the liver sinusoids and returning it to the inferior vena cava. Visceral Surface of the Liver Gallbladder the gallbladder lies in a fossa on the visceral surface of the liver to the right of the quadrate lobe. The common bile duct 112 Chapter 3 l Abdomen, Pelvis, and Perineum penetrates the head of the pancreas where it joins the main pancreatic duct and forms the hepatopancreatic ampulla, which drains into the second part of the duodenum at the major duodenal papilla. BiliaryBiliary Ducts Pancreas the pancreas horizontally crosses the posterior abdominal wall at approximately at the level of the transpyloric plane. It includes the uncinate process which is crossed by the superior mesenteric vessels. The splenic artery undulates along the superior border of the body of the pancreas with the splenic vein coursing posterior to the body. The head of the pancreas receives its blood supply from the superior and inferior pancreaticoduodenal branches of the gastroduodenal and superior mesenteric arteries, respectively. This region is important for collateral circulation because there are anastomoses between these branches of the celiac trunk and superior mesenteric artery. Clinical Correlate Carcinoma of the pancreas commonly occurs in the head of the pancreas and may constrict the main pancreatic duct and the common bile duct. Adult Pancreas Clinical Correlate the spleen may be lacerated with a fracture of the 9th, 10th, or 11th rib on the left side. Spleen the spleen is a peritoneal organ in the upper left quadrant that is deep to the left 9th, 10th, and 11th ribs. The visceral surface of the spleen is in contact with the left colic flexure, stomach, and left kidney. Inasmuch as the spleen lies above the costal margin, a normal-sized spleen is not palpable. The splenic artery and vein reach the hilus of the spleen by traversing the splenorenal ligament. Clinical Correlate A sliding hiatal hernia occurs when the cardia of the stomach herniates through the esophageal hiatus of the diaphragm. The cardiac region receives the esophagus; and the dome-shaped upper portion of the stomach, which is normally filled with air, is the fundus. The pyloric portion of the stomach has a thick muscular wall and narrow lumen that empties into the duodenum approximately in the transpyloric plane (L1 vertebra). Duodenum the duodenum is C-shaped, has 4 parts, and is located retroperitoneal except for the first part. The gastroduode- l Abdomen, Pelvis, and Perineum nal artery and the common bile duct descend posterior to the first part. Smooth muscle in the wall of the duodenal papilla is known as the sphincter of Oddi. Note that the foregut terminates at the point of entry of the common bile duct; the remainder of the duodenum is part of the midgut. Jejunum and Ileum the jejunum begins at the duodenojejunal junction and comprises 2/5 of the remaining small intestine. The beginning of the ileum is not clearly demarcated; it consists of the distal 3/5 of the small bowel. The jejunoileum is suspended from the posterior body wall by the mesentery proper. Although the root of the mesentery is only 6 inches long, the mobile part of the small intestine is approximately 22 feet in length. Colon the cecum is the first part of the colon, or large intestine, and begins at the ileocecal junction. It is a blind pouch, which often has a mesentery and gives rise to the vermiform appendix. It is continuous with the transverse colon at the right (hepatic) flexure of colon. It becomes continuous with the descending colon at the left (splenic) flexure of colon. The midgut terminates at the junction of the proximal two-thirds and distal one-third of the transverse colon. It is the terminal portion of the large intestine and enters the pelvis to continue as the rectum. The superior one-third of the rectum is covered by peritoneum anteriorly and laterally. It is continuous with the rectum at the pelvic diaphragm, where it makes a 90-degree posterior bend (anorectal flexure) below the rectum. The sympathetics (lumbar splanchnics) increase the tone of the muscle and the parasympathetics (pelvic splanchnics) relax the muscle during defecation. Numerous capillaries form extensive networks in the lamina propria (particularly in the small intestine). The muscle confers some motility to the mucosa and facilitates discharge of secretions from glands. In the small intestine, a few strands of smooth muscle may run into the lamina propria and up to the tips of villi. Submucosa the submucosa is a layer of loose areolar connective tissue that attaches the mucosa to the muscularis externa and houses the larger blood vessels and mucous-secreting glands. Muscularis Externa the muscularis externa is usually comprised of 2 layers of muscle: an inner circular and an outer longitudinal. The muscularis externa controls the lumen size and is responsible for peristalsis. Serosa the serosa (or peritoneum of anatomy) is composed of a mesothelium (a thin epithelium lining the thoracic and abdominal cavities) and loose connective tissue. In the abdominal cavity, the serosa surrounds each intestinal loop and then doubles to form the mesentery within which run blood and lymphatic vessels. Clinical Correlate Hirschsprung disease or aganglionic megacolon is a genetic disease present in approximately 1 out of 5,000 live births. It may result from mutations that affect the migration of neural crest cells into the gut. The intrinsic system is capable of autonomous generation of peristalsis and glandular secretions. Sensory fibers accompany the parasympathetic nerves and mediate visceral reflexes and sensations, such as hunger and rectal fullness. The majority of the bacteria in the body-comprising about 500 different species- are in our gut, where they enjoy a rich growth medium within a long, warm tube. Most of these bacteria are beneficial (vitamins B12 and K production, additional digestion, protection against pathogenic bacteria) but a few species of pathogenic microbes appear at times. Mucous and serous secretions of the salivary glands lubricate food, rinse the oral cavity, moisten the food for swallowing and provide partial antibacterial protection. Secretions of IgA from plasma cells within the connective tissue are transported through the gland epithelia to help protect against microbial attachment and invasion. Pharmacology Biochemistry Physiology Medical Genetics Esophagus Pathology Behavioral Science/Social Sciences the esophagus is also lined by a stratified squamous epithelium. In the lower part of the esophagus there is an abrupt transition to the simple columnar epithelium of the stomach. Langerhans cells-macrophage-like antigen-presenting cells-are present in the epithelial lining. The muscularis externa of the esophagus consists of striated muscle in the upper third, smooth muscle in the distal third, and a combination of both in the middle third. The mucosa of the stomach is thrown into folds (rugae) when empty, but disappears when the stomach is full. The stomach begins digestion by initiating the chemical and enzymatic breakdown of ingested food. Proteins are initially denatured by the acidic gastric juice before being hydrolyzed to polypeptide fragments by the enzyme pepsin.

Depending upon the degree of cellular changes antibiotic resistance vietnam order clindamycin online from canada, these abnormal Pap smears will lead to repeated tests at more frequent intervals or require biopsy confirmation with subsequent treatment depending upon the tissue biopsy results virus 360 clindamycin 150 mg on line. The positive note is that most women and men remain symptom-free and clear these viruses with no awareness they had ever been infected virus mutation rate order 300mg clindamycin amex. It is done in parallel with the Pap test in women with a test result with the awkward nomenclature virus 1999 full movie generic 300 mg clindamycin amex, "atypical squamous cells of undetermined significance antimicrobial undershirt 300 mg clindamycin with visa. These biopsies are meant to rule out any more advanced cervical tissue changes than were noted on the cytology report antimicrobial lock solutions cheap 300 mg clindamycin overnight delivery. When either of these two types are present, immediate colposcopy and biopsy are indicated, even in patients with a normal Pap smear. Ten percent of these women will have precancerous lesions even though the Pap smear is normal. Human Papillomavirus Genital Infections 91 Since cervical cancer is an infectious disease, this strategy with a focus upon an already established disease, i. Rather than wait for the appearance of abnormal cervical cellular changes in the Pap smear, these at-risk women would be identified early while they still had a normal Pap smear. The lack of sensitivity and specificity associated with cytologic screening also puts into question the use of the Pap smear as the primary screening intervention. Because of this, they are at greater risk of developing abnormal cervical cytology. In addition, age 30 is a recognizable breakpoint in population studies showing an increasing frequency of invasive cervical cancer as patients age. In the latter situation, they can be returned to a normal population category with cytologic screening at 5-year intervals. The focus remains on cytology, as it has been since the first reports of the potential benefits of cytologic screening in the 1940s. Another future focus will be dependent upon medical treatments to enhance viral clearance. These include the local application of immunomodulators to increase the production of inflammatory cytokines and antiviral substances such as interferon. Local application or injection of interferon has also been used to eliminate these viral infections. Gardasil 9, a vaccine against 6, 11, 16, 18, 31, 33, 45, 52, and 58, was introduced in December 2014. The longterm effectiveness of the first two vaccines has been repeatedly verified in different populations. While three doses of the vaccine are recommended, recent studies have suggested that two or even one dose of the vaccine may have a similar efficacy. Usually, the road to discovery and licensing of a new vaccine against a recognized viral pathogen follows a different and more familiar route. The wild virus pathogen is identified, isolated, and grown on cell culture in the laboratory. After passage through several repetitive cell cultures, a new modified viral strain emerges that, when introduced Vulvovaginal Infections 94 into the human host, confers immunity without causing disease. The bivalent vaccine contains what appears to be a more effective adjuvant that offers cross-protection against the 31 and 45 strains, covering a total of four, while the Gardasil 9 protects against nine strains. The absence of universal health-care coverage in the United States has left too many at-risk segments of the patient population unvaccinated. All three vaccines greatly reduce the likelihood of acquiring cancers resulting from infection. Nearly all cervical cancers can be prevented,41,42 plus 75% of vaginal cancers, 69% of vulvar cancers, and 63% of penile cancers. The decision by the National Health Services in the European Union about which vaccine to use has largely been governed by monetary cost. Gardasil 4 and Gardasil 9 also protect against strains 6 and 11, which cause 90% of condyloma acuminata. Ongoing postlicensure surveillance indicated as of March 2014 that about 67 million vaccine doses had been administered in the United States with only 25,176 adverse events reported to the Vaccine Adverse Event Reporting System, 92% of which were "not serious. Centers for Disease Control and Prevention has reported that adverse event reports peaked within 2 years of the first use of the vaccine and decreased dramatically in each of the subsequent 5 years. Despite these facts, the administration of the vaccine in targeted males and females in the United States ranks far below the levels achieved in Australia and lags far behind the levels achieved with the traditional Tdap (tetanus, diphtheria, acellular pertussis) vaccine. Tdap immunization, first approved in 2005, reached a level in 2013 of 86% in girls and 77. The first attempt at a national health-care plan in the United States, the Affordable Care Act (popularly called "Obamacare," a tag first coined by its critics and then embraced by President Obama and his political allies), is not a nationwide single payer plan but a state-by-state conglomerate that ceded individual immunization decisions to physicians and parents. There has been a spirited and vocal anti-immunization campaign in the United States that extends across the spectrum of vaccines. The recent reemergence of measles, a disease thought to have been eradicated in the United States over a decade ago, illustrates one unintended bad consequence of this anti-vaccine animus. This is the type of a dramatic illustration selected to be shown in most gynecologic textbooks. In many cases, the pathology report confirms that the original clinical diagnosis was in error. The result is that in most cases, the diagnosis is a visual one made at the time of the first visit, when a decision on the type of local therapy is made. For the patients who respond to therapy and whose growths disappear, these limited diagnostic options are not a problem. Most sexually active patients who come for the evaluation of new growths on the perineum or vulva are sure they have "warts," and they are angry and upset with their sexual partners for causing them to develop these visible lesions. It is a sensitive test system that will be positive if 5000 or more copies of the virus are present in the sample. It is simple for the laboratory to perform and easy for the clinician as well, done in conjunction with the collection of a liquid-based Pap smear specimen. The test has shortcomings that can make interpretation of the results difficult for both the physician and the patient. The lesions were removed under local anesthesia with the pathologic diagnosis of an angiokeratoma. Patients with micropapillomatosis labialis are often assumed to have genital warts. A clinical tip-off Vulvovaginal Infections 98 when the patient is first tested, the patient can be shedding large quantities of virus. When a follow-up Hybrid Capture test is obtained later in the course of infection, although the number of shed viral particles is much smaller, the result is still a yes. The positive report gives the physicians no hint as to whether the numbers of shed viral particles are decreasing. The test also can be confusing to the patient and the physician in the event that a patient who originally tested positive remains positive. One study found the number of cases at risk for these falsepositive tests to be less than 3%. Of more concern is overtreatment, which can result in ugly scarring because of damage to adjoining normal tissue. A potential problem is the occasional inability of the practitioner to measure the depth of the burn at the time of treatment, resulting in damage to the underlying tissue and subsequent scar formation. Finally, laser has the appeal of a high-technology approach with better control of the depth of the burn. Laser also requires major capital investment, and some physicians may be tempted to overuse this expensive mode of therapy. There are medical treatments for these visible lesions that can be used by the physicians. If this approach is selected, podophyllin resin in tincture of benzoin can be applied directly to each wart and allowed to dry. There are legitimate concerns about the increasing concentration of these tissue-toxic resins over time while stored in the office, plus the normal tissue reaction if any medication runs off the wart to adjoining normal skin. Again, the concern is the risk of spillage of either these acids onto normal integument with burning and subsequent scarring, and the treatment site needs to be washed several hours after treatment. It is the sublesional injection of one million units of interferon, because successful treatment results in the elimination of the warts without residual scarring. For one, it requires many office visits, and several weeks must elapse after the last injection to determine if the treatment has been effective. Every woman will have systemic symptoms after the first injection, such as general body aches and fever. In addition, even though the amount of medication to be injected is small, it is painful when inoculated into this sensitive perineal area. A convenient first choice for treatment of small perineal condyloma acuminata on cornified epithelium is patient-applied therapy. A wide range of therapeutic choices exists when these new growths are found on the cornified squamous epithelium of the perineum. The normal tissue adjacent to these "warts" is more tolerant of any destructive therapy that inevitably extends to the normal tissue beyond the wart. In contrast, damage to the normal mucous membranes must be avoided at all cost because of the long-term morbidity associated with mucous membrane scarring. For rapid elimination of these new unwanted tissue growths on cornified epithelium, a number of options are available. Freezing the lesions with liquid nitrogen or a cryoprobe requires training with the use of this modality, and frequent employment of the probe is needed for the physician to maintain competence. Unless this is done, the result can be suboptimal treatment that does not completely destroy the warts and that requires future office visits for Human Papillomavirus Genital Infections 99 local therapy repeatedly without visit after visit to the physician. Patients use the local application of 5% imiquimod cream directly to the warts on Monday, Wednesday, and Friday evenings for four consecutive weeks. The beauty of this treatment is that when successful, the warts disappear without residual scars. In some women, the warts proliferate to the extent that the vaginal introitus becomes a mass of friable tissue, an unfavorable site with the tissue lacerations of vaginal delivery. These large friable exophytic lesions should not be treated with podophyllin resin, because their large area of absorption permits systemic toxicity for both the mother and the fetus. Observation is not an option, for the other concern is that pregnant women with genital warts have 231. In these cases, the vulva should be reexamined at each subsequent prenatal visit, for recurrences are not uncommon. They have more frequent recurrences following therapy and squamous cell carcinoma arising in or resembling genital warts may occur. These growths should be removed either by scalpel or hot wire loop excision under local anesthesia with the tissue sent to pathology for microscopic evaluation and diagnosis. Patients with lesions on the mucosa of the labia minora, vagina, or cervix pose a different set of treatment problems for the physician. Tissue fulguration therapy (successfully used with the more resilient cervical tissue) when applied to the more sensitive mucosal membranes of the vagina and vulva can cause scarring with a subsequent quality-of-life issue and dyspareunia. The patient needs to be followed to check for recurrences, but, usually, the cervix heals and the patient is free of problems. Applying the same regimen to the mucosa of the labia minora or vagina can result in tissue injury and scarring with long-term adverse sexual ramifications. These reactions are seen to an even greater extent in the vagina where the removal of the speculum after treatment allows transfer of these irritating medications to normal vaginal mucosa with a potential for a mucosal burn. A popular therapy for vaginal warts in the 1970s was the intravaginal use of 5-fluorouracil cream. The long-term problems seen in patients who had this treatment are the result of too-long sequestration of this irritant in the posterior vaginal cul-de-sac with ulceration and subsequent scar formation. A small biopsy under local anesthesia should be done to confirm the diagnosis of condyloma acuminata. Once this diagnosis is confirmed, the use of intralesional injection of one million units of interferon will speed up the process of wart elimination by the human host and avoids the problem of residual scar formation, but it has all the difficulties previously noted with this method of therapy, including frequent office visits and patient discomfort. The current pathway of care is colposcopy with biopsy of any abnormal areas noted by acetic acid and iodine staining. More than 70% of the women whose margins were not free of tissue abnormalities reverted to normal over time with no further therapy. They have been noted to have high rates of recurrent and persistent cervical intraepithelial neoplasia. Imiquimod, agents similar to imiquimod, and the local application of an interferon gel or the local injection of interferon have the potential to accelerate the elimination of these viruses. They may be part of the new therapeutic strategy, targeting the pathogen, not the Pap smear results. Obviously, prospective studies will be necessary to ascertain the efficacy of such an approach. Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Effect of male circumcision on the prevalence of high-risk human papillomavirus in young men: Results of a randomized controlled trial conducted in Orange Farm, South Africa. Persistence of type-specific human papillomavirus infection among cytologically normal women. Disparity in the persistence of high-risk human papillomavirus genotypes between African American and European American women of college age.

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