Marilia Cascalho, MD, PhD

• Professor of Surgery and Professor of Microbiology and
• Immunology, Transplantation Biology
• Associate
• Professor of Surgery and Associate Professor of
• Microbiology & Immunology, Transplantation Biology,
• University of Michigan, Ann Arbor, MI
• Emerging Strategies in Kidney Transplantation

You can also call our Information Specialists for information about clinical trials anxiety remedies buy generic asendin 50 mg on line, or use our free clinical trial service at Other side efects may be serious and last a long time anxiety jaw muscle tension purchase asendin 50 mg on-line, but they usually go away once treatment ends depression extreme fatigue best asendin 50 mg. Aranesp and Procrit are drugs that might be given to increase the red blood cell count mood disorder lecture order generic asendin canada. Other side efects of treatment may include {{Extreme tiredness {{Fever {{Cough {{Rash {{Hair loss {{Weakness {{Tingling sensation {{Lung, heart or nerve problems. Patients should talk with their doctors about any longterm or late efects that may be related to their treatment. Children and adults who have been treated for lymphoma should see their primary care doctor and an oncologist (cancer specialist) for followup care. You can ask what tests your doctor will need and fnd out how often to have the tests. It is important to get a record of the cancer treatment you received so that your doctor can follow up on specifc longterm efects that may be associated with your treatment. To fnd a followup clinic and other resources for child and adult survivors, contact our Information Specialists. Tracking Your Lymphoma Tests Tese tips may help you save time and know more about your health. The Lymphoma Guide I page 39 L Medical Terms For longer defnitions of words or for defnitions of words you do not see in this section, visit A liquid sample containing cells is taken from the marrow and then the cells are looked at under a microscope. Examples of foreign material are an infectioncausing microorganism, a vaccine or the cells of another person used for an allogeneic stem cell transplant. A treatment that uses antibodies to carry a radioactive substance to lymphoma cells to kill them. No sign of the disease and/or a period of time when the disease is not causing any health problems. A type of cell found in marrow that makes red blood cells, white blood cells and platelets. The low magnifcation images should be used for orientation, while the higher magnifcation images show details of cells, tissues, and organs. Al though every effort has been made to faithfully reproduce the colors of the tissues, a full appreciation of histological structure is best achieved by examining the original speci mens with a microscope. The photomicrographs found in this atlas come from the collection of microscope slide used by medical, dental and undergraduate students of histology at the University of Minnesota. Each tissue specimen, in its entirety, has been digitized with a high resolution 40X or 60X lens to generate virtual microscope slides. The Virtual Microscope Collection includes additional slides which complement and extend the core slide collection. Pro ducing the virtual slide collection and developing the web site for their presentation was done with the very capable assistance of Todd C. Her talented interpretation of biological structure and its artistic rendering greatly facilitate the learning and comprehension of histology. Histology is the study of cells, tissues and organs as seen through the micro Examination of tissues requires that they be pre scope. This is a structure that can be observed through the light multistep process that includes fxation (preserves microscope, histology also includes cellular detail the tissue), embedment (stabilizes the tissue for down to the molecular level that can be observed sectioning), sectioning (cuts the specimen into thin using an electron microscope. The importance of slices of about 5 um) then placing the sections on a histology is that it is the structural basis for cell, glass slide so they can be stained for viewing. For the light microscope with optimal lenses and sample preparation this What is the plan for the study of cells, tissues and approaches 0. Epithelium to detect something and this can be much smaller than the limit of resolution. Nervous tissue Most cells 1030 um Chapters 28 are concerned with the features of Red blood cell 7 um the four basic tissues. Microvillus 100 nm Electron Micro scope the light microscope, tissue preparation, limits and challenges. Microtubule 24 nm Myosin flaments 15 nm the bright feld light microscope is a two lens com pound optical instrument. The oculars have a 10 ments fold magnifcation and the objectives range from Plasma mem 9 nm 10X, 20X, 40X to 100X. In Microflaments 5 nm practice this means that while using the 10X objec (actin) tive you have a wide feld of view, but with low reso lution. While using the 100X objective you have high resolution, but with a very small feld of view. There are several challenges in learning histol To use a metaphor what this means is that when ogy. The frst being that the view observed through using the low power objective you can see the for a microscope gives you a perspective that you est but not the trees and while using the high power are unlikely to have experienced previously. Therefore when examining a speci shapes and sizes, with varying shades of red and men it is essential to start with the low power ob blue. This complex image offers very few clues jective to gain perspective and then work up to the that are intuitive. Also, the tissue specimen is a two highest power magnifcation as needed to observe dimensional slice of a complex three dimensional the necessary detail. So, once the two dimensional image How to take Histology Laboratory Notes: has been ascertained you still have the challenge of imagining its three dimensional elaboration. Write notes about its appearance, characteris ways possible, this atlas was written as if a teacher tics and features. The next task in learning is to see if you can identify the structures when examin b. Verhoeff: stains elastic protein black logical tissue specimens through the microscope. Aldehyde fuchsin: stains insulin, mast cell and provides little to see in the standard bright granules and elastic fbers purple feld microscope unless treated with a histological stain. It is divided into three histologic Adventitia or serosa: this outermost layer is regions: cardiac, fundus/body and pyloric. When it blends small intestine is the principle site for digestion and with connective tissue of the surrounding area it is absorption. If it has a free surface projecting the large intestine and is divided into three regions: into the peritoneal cavity it is covered with a single duodenum, jejunum and ileum. The large intestine layer of mesothelial cells (epithelial cells derived has the main function of reabsorbing water from from mesoderm) and is called a serosa. The parts of the large intestine are the esophagus cecum, appendix, colon, rectum and anal canal. The epithelium is stratifed squamous and nonker general plan for hollow Tubular organs atinized. This is supported by a lamina the walls of hollow organs have four layers or tu propria. A well developed muscularis mucosa is nics: mucosa, submucosa, muscularis externa and present (200300 um) and surrounded by the sub adventitia or serosa. The muscularis externa Mucosa (mucous membrane): Mucous mem consists of an inner circular layer and an outer lon branes line internal passages and provide a barrier gitudinal layer. In the upper third of the esophagus between the tissues of the body and the external the muscularis is skeletal muscle. The membranes are constantly wet third both smooth and skeletal muscle is present and lubricated by mucus. The mucosa has three and in the lower third only smooth muscle is pres parts: an epithelium, lamina propria and muscu ent. When glands are An abrupt transition occurs at the cardioesoph found in this layer they are referred to as mucosal ageal junction, where stratifed squamous epi glands. The muscularis mucosa, when present, thelium gives way to simple columnar epithelium.

Diseases

• Amelogenesis imperfecta hypomaturation type
• Scott syndrome
• Arthritis, juvenile
• Faulk Epstein Jones syndrome
• Onat syndrome
• Mental retardation anophthalmia craniosynostosis

Most reported cases are sporadic definition for depression in economics purchase discount asendin line, but widespread outbreaks depression movies purchase line asendin, includ ing health careassociated and institutional outbreaks depression test short cheap 50 mg asendin, have been reported depression video game buy discount asendin on-line. The incidence of nontyphoidal Salmonella gastroenteritis has diminished little in recent years, in contrast to other enteric infections of bacterial etiologies. Every year, nontyphoidal Salmonella organisms are one of the most common causes of laboratoryconfrmed cases of enteric disease reported by the Foodborne Diseases Active Surveillance Network (FoodNet [ A potential risk of transmission of infection to others persists for as long as an infected person excretes nontyphoidal Salmonella organisms. Twelve weeks after infection with the most common nontyphoidal Salmonella serotypes, approximately 45% of children younger than 5 years of age excrete organisms, compared with 5% of older children and adults; antimicrobial therapy can prolong excretion. Approximately 1% of adults con tinue to excrete Salmonella organisms for more than 1 year. Diagnostic tests to detect Salmonella antigens by enzyme immunoassay, latex agglutination, and monoclonal anti bodies have been developed, as have assays that detect antibodies to antigens of enteric fever serotypes. Genebased polymerase chain reaction diagnostic tests also are available in research laboratories. The sensitivity of blood culture and bone marrow culture in children with enteric fever is approximately 60% and 90%, respectively. The combination of a single blood culture plus culture of bile (collected from a bilestained duodenal string) is 90% in detecting Salmonella serotype Typhi infection in children with clinical enteric fever. Resistance to these antimicrobial agents is becoming more common, especially in resourcelimited countries. In areas where ampicillin and trimethoprimsulfamethoxazole resistance is common, a fuoroquinolone or azithromycin usually is effective. However, fuoroquino lones are not approved for this indication in people younger than 18 years of age (see Fluoroquinolones, p 800). Once antimicrobial susceptibility test results are available, ampicillin or ceftriaxone for susceptible strains is recommended for at least 4 to 6 weeks. Drugs of choice, route of administration, and duration of therapy are based on susceptibility of the organism (if known), knowledge of the anti microbial susceptibility patterns of prevalent strains, site of infection, host, and clinical response. Multidrugresistant isolates of Salmonella serotypes Typhi and Paratyphi A and strains with decreased susceptibility to fuoroquinolones are common in Asia and are found increasingly in travelers to areas with endemic infection. Invasive salmonel losis attributable to strains with decreased fuoroquinolone susceptibility is associated with greater risk for treatment failure. Salmonella serotypes Typhi and Paratyphi A and nontyphoidal Salmonella isolates with ciprofoxacin resistance or that produce extended spectrum betalactamases occasionally are reported. Empiric treatment of enteric fever with ceftriaxone or fuoroquinolone is recommended, but once antimicrobial sus ceptibility results are known, therapy should be changed as necessary. Azithromycin is an effective alternative for people with uncomplicated infections. Aminoglycosides are not recommended for treatment of invasive Salmonella infections. The chronic carrier state may be eradicated by 4 weeks of oral therapy with ciprofoxacin or norfoxacin, antimicrobial agents that are highly concen trated in bile. Highdose parenteral ampicillin also can be used if 4 weeks of oral fuo roquinolone therapy is not well tolerated (see Fluoroquinolones, p 800). Cholecystectomy may be indicated in some adults if antimicrobial therapy alone fails. These drugs should be reserved for critically ill patients in whom relief of manifestations of toxemia may be life saving. The usual regimen is highdose dexamethasone given intravenously at an initial dose of 3 mg/kg, followed by 1 mg/kg, every 6 hours, for a total course of 48 hours. In children with typhoid fever, precautions should be continued until culture results for 3 consecutive stool specimens obtained at least 48 hours after cessation of antimicro bial therapy are negative. Notifcation of public health authorities and determination of serotype are of primary importance in detection and investigation of outbreaks. Specifc strategies for controlling infection in outofhome child care include adherence to hygiene practices, including meticulous hand hygiene and limiting exposure to reptiles and rodents (see Children in OutofHome Child Care, p 133). When nontyphoidal Salmonella serotypes are identifed in a symptomatic child care attendee or staff member with enterocolitis, older children and staff members do not need to be excluded unless they are symptomatic. Stool cultures are not required for asymptomatic contacts or for return to child care following resolution of illness. Antimicrobial therapy is not recommended for people with asymptomatic nontyphoi dal Salmonella infection or uncomplicated diarrhea or for people who are contacts of an infected person. When Salmonella serotype Typhi infection is identifed in a child care staff member, local or state health departments may be consulted regarding regulations for length of exclusion and testing, which may vary by jurisdiction. Resistance to infection with Salmonella serotype Typhi is enhanced by typhoid immunization, but currently licensed vaccines do not provide complete protec tion. Vaccine is selected on the basis of age of the child, need for booster doses, and possible contraindications (see Precautions and Contraindications, p 640) and reactions (see Adverse Events, p 640). In the United States, immunization is recommended only for the following people: Travelers to areas where risk of exposure to Salmonella serotype Typhi is recognized. Risk is greatest for travelers to the Indian subcontinent, Latin America, Asia, the Middle East, and Africa who may have prolonged exposure to contaminated food and drink. Such travelers need to be cautioned that typhoid vaccine is not a substitute for careful selection of food and drink (see For primary immunization, the following dosage is recommended for each vaccine: Typhoid vaccine live oral Ty21a (Vivotif). Children (6 years of age and older) and adults should take 1 entericcoated capsule every other day for a total of 4 capsules. The capsules should be kept refrigerated, and all 4 doses must be taken to achieve maximal effcacy. Commercially Available Typhoid Vaccines in the United States Minimum Age of Booster Adverse Typhoid Receipt, No. Results of 2 feld trials suggest that Ty21a may provide partial crossprotection against Salmonella serotype Paratyphi B. In circumstances of continued or repeated exposure to Salmonella serotype Typhi, periodic reimmunization is recommended to maintain immunity. Continued effcacy for 7 years after immunization with the oral Ty21a vaccine has been demonstrated; however, the manufacturer of oral Ty21a vaccine recommends reimmunization (completing the entire 4dose series) every 5 years if continued or renewed exposure to Salmonella serotype Typhi is expected. No data have been reported concerning use of one vaccine administered after primary immunization with the other. The oral Ty21a vaccine produces mild adverse reactions that may include abdominal discomfort, nausea, vomiting, fever, headache, and rash or urticaria. No data are available regarding effcacy of typhoid vaccines in children younger than 2 years of age. The oral Ty21a vaccine requires replication in the gut for effectiveness; it should not be administered during gastrointestinal tract illness. Studies have demonstrated that simultaneous administration of either mefoquine or chlo roquine with oral Ty21a results in an adequate immune response to the vaccine strain. However, if mefoquine is administered, immunization with Ty21a should be delayed for 24 hours. Also, the antimalarial agent proguanil should not be administered simultane ously with oral Ty21a vaccine but, rather, should be administered 10 or more days after the fourth dose of oral Ty21a vaccine. Antimicrobial agents should be avoided for 24 or more hours before the frst dose of oral Ty21a vaccine and 7 days after the fourth dose of Ty21a vaccine. In older children and adults, the sites of predilection are interdigital folds, fexor aspects of wrists, extensor surfaces of elbows, anterior axillary folds, waistline, thighs, navel, genitalia, areolae, abdo men, intergluteal cleft, and buttocks. In children younger than 2 years of age, the erup tion generally is vesicular and often occurs in areas usually spared in older children and adults, such as the scalp, face, neck, palms, and soles. The eruption is caused by a hyper sensitivity reaction to the proteins of the parasite. Characteristic scabietic burrows appear as gray or white, tortuous, threadlike lines. Excoriations are common, and most burrows are obliterated by scratching before a patient is seen by a physician. Occasionally, 2 to 5mm redbrown nodules are present, particularly on covered parts of the body, such as the genitalia, groin, and axilla.

History of trauma or pain and the amount and character of the bleeding should be assessed depression brochure order asendin 50 mg. Speculum and digital pelvic examination should not be done until placenta previa has been excluded resistant depression definition buy generic asendin 50 mg on-line. KleihauerBetke test of maternal blood is used to quantify fetal to maternal hemorrhage depression zodiac buy discount asendin 50mg online. Placental abruption (abruptio placentae) is defined as complete or partial placental separation from the decidua basalis after 20 weeks gestation depression definition lexikon order asendin uk. Preterm premature rupture of the membranes 274 Bleeding in the Second Half of Pregnancy 10. Rapid uterine decompression after delivery of the first fetus in a twin gestation or rupture of membranes with polyhydramnios 11. Abruption is characterized by vaginal bleeding, abdominal pain, uterine tenderness, and uterine contractions. Pain is usually of sudden onset, constant, and localized to the uterus and lower back. Localized or generalized uterine tenderness and increased uterine tone are found with severe placental abruption. An increase in uterine size may occur with placental abruption when the bleeding is concealed. Concealed bleeding may be detected by serial measurements of abdominal girth and fundal height. Uterine contractions by tocodynamometry is the most sensitive indicator of abruption. Cryoprecipitate contains 250 mg fibrinogen/unit; 4 gm (1520 U) is an effective dose. Vaginal delivery is expedited in all but the mildest cases once the mother has been stabilized. Cesarean section is indicated for fetal distress, severe abruption, or failed trial of labor. Placenta previa occurs when any part of the placenta implants in the lower uterine segment. Ninety percent of placenta previas diagnosed in the second trimester resolve spontaneously. Total placenta previa occurs when the internal cervical os is completely covered by placenta. Partial placenta previa occurs when part of the cervical os is covered by placenta. Marginal placenta previa occurs when the placental edge is located within 2 cm of the cervical os. Placenta previa presents with a sudden onset of painless vaginal bleeding in the second or third trimester. The initial bleeding usually resolves spontaneously and then recurs later in pregnancy. In a pregnancy $36 weeks with documented fetal lung maturity, the neonate should be immediately delivered by cesarean section. Low vertical uterine incision is probably safer in patients with an anterior placenta. If severe hemorrhage jeopardizes the mother or fetus, cesarean section is indicated regardless of gestational age. Expectant management is appropriate for immature fetuses if bleeding isnotexcessive, maternalphysicalactivitycanberestricted, intercourse and douching can be prohibited, and the hemoglobin can be maintained at $10 mg/dL. PregnancyInduced Hypertension Women with hypertension during pregnancy typically present with few or no symptoms. Chronic hypertension is defined as hypertension before the pregnancy or early in the pregnancy. Blood pressure normally declines during the first trimester and reaches a nadirat20weeksgestation. Daughters and sisters of women with a history of pregnancyinduced hypertension have an increased risk for the condition. Preeclampsia is more common in women with chronic hypertension or chronic renal disease. Other risk factors include diabetes, antiphospholipid antibody syndrome and molar pregnancy. The onset of signs and symptoms of pregnancyinduced hypertension is usually after 20 weeks gestation B. The classic triad of preeclampsia consists of hypertension, edema and proteinuria. A 24hour urine collection that shows more than 300 mg protein per 24 hours is significant. However, edema is also extremely common in normal pregnancies during the third trimester. Generalized edema is more significant than dependent edema occurring only in the lower extremities. Weight gain of greater than 1 to 2 lb per week may indicate significant fluid retention. In normal pregnancies, the uric acid level declines during pregnancy and then returns to baseline by term. Decreased renal perfusion may be indicated by the presence of creatinine levels at term that are the same as normal prepregnancy levels. Severe pregnancyinduced hypertension is indicated by symptoms of headache, blurred vision or abdominal pain in combination with elevated blood pressure. Clinical evaluation of pregnancyinduced hypertension should include symptoms of headache, visual disturbances and abdominal pain. The physical examination should include evaluation of theheart, lungsandabdomen, andneurologicsystem. An ultrasound to assess fetal weight and gestational age should verify adequate fetal growth. Women with mild elevations in blood pressure and proteinuria but no evidenceofseveresignsorsymptomsmaybesafelyobservedwithout immediate treatment or delivery. Women with mild preeclampsia at term should be considered candidates for induction of labor. Mild elevations in blood pressure (<170 mmHg systolic or <105 mmHg diastolic) do not require treatment with antihypertensive medications. Initial evaluation may take place in the hospital with fetal monitoring, 24hour urine collection and monitoring for progression of disease. All women managed as outpatients should be instructed to contact the physician if any symptoms of severe pregnancyinduced hypertension appear. Followup should include tests for proteinuria, blood pressure assessment, home health care nursing and frequent clinic visits. Monitoring of fetal growth and amniotic fluid index is initiated at 30 to 32 weeks. Treatment for women at earlier gestations (28 to 34 weeks) consists of conservative observation or immediate delivery.

They usually are small mood disorder nos dsm 4 criteria best 50 mg asendin, multiple anxiety 5 htp generic 50 mg asendin, and fat topped; seldom exhibit papillomatosis; and rarely cause pain anxiety chest pains purchase asendin paypal. Anogenital warts mood disorder risperdal generic asendin 50mg otc, also called condylomata acuminata, are skincolored warts with a caulifowerlike surface that range in size from a few millimeters to several centimeters. In males, these warts may be found on the penis, scrotum, or anal and perianal area. In females, these lesions may occur on the vulva or perianal areas and less commonly in the vagina or on the cervix. Anogenital warts often are multiple and attract attention because of their appearance. Warts usually are painless, although they may cause itching, burning, local pain, or bleeding. Juvenile recurrent respiratory papillomatosis is a rare condition character ized by recurring papillomas in the larynx or other areas of the upper respiratory tract. This condition is diagnosed most commonly in children between 2 and 5 years of age and manifests as a voice change, stridor, or abnormal cry. Most appear during the frst decade of life, but malignant transformation, which occurs in 30% to 60% of affected people, usually is delayed until adulthood. These viruses are grouped into cutaneous and mucosal types on the basis of their tendency to infect particular types of epithelium. More than 14 highrisk types are recognized, with types 16 and 18 most frequently being associated with cervical cancer and type 16 most frequently being associated with other anogenital cancers and oropharyngeal cancers. Types 6 and 11 frequently are associated with condylomata acuminata, recurrent respiratory papillomatosis, and conjunctival papillomas. Cutaneous warts occur commonly among schoolaged children; the prevalence rate is as high as 50%. An increase in the incidence of plantar warts has been associ ated with swimming in public pools. The intense and often widespread appearance of cutaneous warts in patients with compromised cellular immunity (particularly patients who have undergone transplantation and people with human immunodefciency virus infection) suggests that alterations in immunity predispose to reactivation of latent intraepithelial infection. Rarely, infection is transmitted to a child through the birth canal during delivery or transmitted from nongenital sites. Respiratory papillomatosis is believed to be acquired by aspiration of infectious secretions during passage through an infected birth canal. When anogenital warts are identifed in a child who is beyond infancy but is prepubertal, sexual abuse must be considered. The incubation period is unknown but is estimated to range from 3 months to several years. Papillomavirus acquired by a neonate at the time of birth may never cause clinical disease or may become apparent over several years (eg, respiratory papilloma tosis). Anogenital and pharyngeal malignant neoplasias are rare longterm sequelae of chronic persistent infection, usually occurring more than 10 years after infection. Cervical dysplasias may be detected via (1) cytologic examination of exfoliated cells in a Pap test, either by conventional or liquidbased cytologic methods; or (2) histologic examination of cervical tissue biopsy. These tests are recommended by some organizations for use in combination with Pap testing in women 30 years of age or older and for triage of women 20 years of age or older in specifc circumstances to help determine whether further assessments, such as colposcopy, are necessary (American Society for Colposcopy and Cervical Pathology guidelines, 2006 algorithm [ Treatment of anogenital warts may differ from treat ment of cutaneous nongenital warts, so treatment options for these warts should be dis cussed with a health care professional. The optimal treatment for genital warts that do not resolve spontaneously has not been identifed. Most nongenital warts eventually regress spon taneously but can persist for months or years. Most methods of treatment use chemical or physical destruction of the infected epithelium, including application of salicylic acid products, cryotherapy with liquid nitrogen, or laser or surgical removal of warts. Daily treatment with tretinoin has been useful for widespread fat warts in children. Pharmacologic treatments for refractory warts, including cimetidine, have been used with varied success. Treatments are characterized as patient applied or administered by health care pro fessionals and include ablational/excisional treatments, antiproliferative methods, and immunemodulating therapy. Many of the agents used for treatment have not been tested for safety and effcacy in children, and some agents are contraindicated in pregnancy. Recurrences are common and may be attributable to reactivation rather than reinfection. This approach rec ognizes the importance of avoiding unnecessary treatment for cervical dysplasia, which can have substantial economic, emotional, and reproductive adverse effects, including higher risk of preterm birth. Sexually active female adolescents who have had an organ transplant or are receiving longterm corticosteroid therapy also should undergo similar cervical Pap test screening. If cytologic screening has been initiated before 21 years of age, patients with abnormal Pap test results should be cared for by a physician who is knowledgeable in the management of cervical dysplasia. Respiratory papillomatosis is diffcult to treat and is best managed by an otolaryngolo gist. Local recurrence is common, and repeated surgical procedures for removal often are necessary. Extension or dissemination of respiratory papillomas from the larynx into the trachea, bronchi, or lung parenchyma can result in increased morbidity and mortality; rarely, carcinoma can occur. Intralesional interferon, indole3carbinole, photodynamic therapy, and intralesional cidofovir have been used as investigational treatments and may be of beneft for patients with frequent recurrences. Oral warts can be removed through cryotherapy, electrocautery, or surgical excision. In addition, use of latex condoms has been associated with a decrease in the risk of genital warts and 1 American College of Obstetricians and Gynecologists. The degree and duration of contagiousness in patients with a history of genital infection is unknown. Sex partners of people with genital warts may ben eft from examination to assess for the presence of anogenital warts or other sexually transmitted infections. Antibody concentrations decrease over time after the third dose but plateau by 18 to 24 months after receipt of the third dose for either vaccine. However, the clinical signifcance of antibody levels is not clear, because a serologic correlate of protection has not been established. Longterm followup studies are being conducted to determine the duration of effcacy for both vaccines. Vaccine also is recommended for females 13 through 26 years of age not previously immunized. The second dose should be administered 1 to 2 months after the frst dose, and the third dose should be administered 6 months after the frst dose. The minimum interval between doses 2 and 3 is 12 weeks (and at least 24 weeks after the frst dose). The immune response and vaccine effcacy in immunocompromised people might be less than that in immunocompetent people. The health care pro fessional should inquire about pregnancy in sexually active patients, but a pregnancy test is not required before starting the immunization series. If a vaccine recipient becomes pregnant, subsequent doses should be postponed until the postpartum period. If a dose has been administered inadvertently during pregnancy, no action is recom mended. Clinical patterns are categorized as an acute subacute form that predominates in childhood and a chronic form that is the typical clinical pattern in adults. In both forms, constitutional symptoms, such as fever, malaise, and weight loss, are com mon. Oral, upper respira tory tract and gastrointestinal tract granulomatous or ulcerative mucosal lesions are less common manifestations of disease in children than in adults. The mode of transmission is unknown; persontoperson transmission does not occur. A number of serologic tests are available; quantitative immunodiffusion is the preferred test.

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