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Aurogra

By J. Lukar. University of California, Berkeley.

Here we have a levels of factor A , b levels of factor B , and n observations for each combination of levels . Each of the ab combinations of levels of factor A with levels of factor B is a treatment . An alternative arrangement of the data would be obtained by listing the observations of each treatment in a separate column . Note the similarity of the data display for the factorial experiment as shown in Table 8 . The factorial experiment , in order that the experimenter may test for interaction , requires at least two observations per cell , whereas the randomized complete block design requires only one observation per cell . We use two-way analysis of variance to analyze the data from a factorial experiment of the type presented here. For a discussion of other designs, consult the references at the end of this chapter. The Model The fixed-effects model for the two-factor completely randomized design may be written as xijk ¼ m þ ai þ bj þ ab ij þ eijk (8. The observations in each of the ab cells constitute a random independent sample of size n drawn from the population defined by the particular combination of the levels of the two factors. In this case they select the hypothesis they wish to test, choose a significance level a, and proceed in the familiar, straightforward fashion. This procedure is free of the complications that arise if the researchers wish to test all three hypotheses. When all three hypotheses are tested, the situation is complicated by the fact that the three tests are not independent in the probabilistic sense. If we let a be the significance level associated with the test as a whole, and a0; a00; and a000 the significance levels associated with hypotheses 1, 2, and 3, respectively, we find 0 00 000 a < 1 À 1 À a 1 À a 1 À a (8. This means that the probability of rejecting one or more of the three hypotheses is less than. To demonstrate the hypothesis testing procedure for each case, we perform all three tests. The reader, however, should be aware of the problem involved in interpreting the results. When H0 is true and the assumptions are met, each of the test statistics is distributed as F. Reject H0 if the computed value of the test statistic is equal to or greater than the critical value of F. By an adaptation of the procedure used in partitioning the total sum of squares for the completely randomized design, it can be shown that the total sum of squares under the present model can be partitioned into two parts as follows: X X Xa b n X X Xa b n ÀÁX X Xa b n 2 2 2 ðxijk À x... If the assumptions stated earlier hold true, and if each hypothesis is true, it can be shown that each of the variance ratios shown in Table 8. A record was made also of each nurse’s age and the type of illness of each patient visited. The researchers wished to obtain from their investigation answers to the following questions: 1. The data on length of home visit that were obtained during the study are shown in Table 8. To analyze these data, we assume a fixed-effects model and a two-factor completely randomized design. For our illustrative example we may test the following hypotheses subject to the conditions mentioned above. When H0 is true and the assumptions are met, each of the test statistics is distributed as F. Reject H0 if the computed value of the test statistic is equal to or greater than the critical value of F. The critical values of F for testing the three hypotheses of our illustrative example are 2. Since denominator degrees of freedom equal to 64 are not shown in Appendix Table G, 60 was used as the denominator degrees of freedom. We put the measurements in Column 1, the row (factor A) codes in Column 2, and the column (factor B) codes in Column 3. When H0: a1 ¼ a2 ¼ a3 ¼ a4 is rejected, we conclude that there are differences among the levels of A, that is, differences in the average amount of time spent in home visits with different types of patients. Similarly, when H0: b1 ¼ b2 ¼ b3 ¼ b4 is rejected, we con- clude that there are differences among the levels of B, or differences in the average amount of time spent on home visits among the different nurses when grouped by age. When H0: ðabÞij ¼ 0 is rejected, we conclude that factors A and B interact; that is, different combinations of levels of the two factors produce different effects. When the hypothesis of no interaction is rejected, interest in the levels of factors A and B usually become subordinate to interest in the interaction effects. In other words, we are more interested in learning what combinations of levels are significantly different. When the number of observations per cell is not the same for every cell, the analysis becomes more complex. Cell death caused by stroke partially results from the accumulation of high concentrations of glutamate. Four rats were studied at each dose and ion level, and the mea- sured variable is the percent of cell death as compared to glutamate. Researchers at a trauma center wished to develop a program to help brain-damaged trauma victims regain an acceptable level of independence. An experiment involving 72 subjects with the same degree of brain damage was conducted. The objective was to compare different combinations of psychiatric treatment and physical therapy. Each subject was assigned to one of 24 different combinations of four types of psychiatric treatment and six physical therapy programs. The response variable is the number of months elapsing between initiation of therapy and time at which the patient was able to function independently. Can one conclude that there is interaction between psychiatric treatment programs and physical therapy programs? Yet, there is a lack of evidence as to whether advice given to sufferers is effective and what improvements may be expected in the conditions. Subjects in the intervention group received health education from a nurse, while the control group did not receive education. In the 6 months between pre- and post-evaluation, the subjects kept a headache diary. The following table gives as the response variable the difference (pre – post) in frequency of headaches over the 6 months for two factors: (1) treatment with two levels (intervention and control), and (2) migraine status with two levels (migraine sufferer and nonmigraine sufferer). Dowson,“ManagementbyNursesofPrimary Headache: A Pilot Study,” Current Medical Research Opinion, 18 (2002), 471–478. Can one conclude on the basis of these data that there is a difference in the reduction of headache frequency between the control and treatment groups? Can one conclude that there is a difference in the reduction of headache frequency between migraine and non-migraine sufferers? Can one conclude that there is interaction between treatments and migraine status? Subjects were classified as having fewer than 50 copies/ml (plasma 1) or having 50 or more copies/ml (plasma 2). Can you think of any extraneous variables whose effects are included in the error term? During the fall allergy season, 172 subjects were randomly assigned to receive treatments of desloratadine and 172 were randomly assigned to receive a placebo. Subjects took the medication for 2 weeks after which changes in the nasal symptom score were calculated. A significant reduction was noticed in the treatment group compared to the placebo group, but gender was not a significant factor. Two experimental designs, the completely randomized and the randomized complete block, are discussed in considerable detail. In addition, the concept of repeated measures designs and a factorial experiment as used with the completely randomized design are introduced. Individuals who wish to pursue further any aspect of analysis of variance will find the methodology references at the end of the chapter most helpful. For each of the following designs describe a situation in your particular field of interest where the design would be an appropriate experimental design. Use real or realistic data and do the appropriate analysis of variance for each one: (a) Completely randomized design (b) Randomized complete block design (c) Completely randomized design with a factorial experiment (d) Repeated measures designs ÀÁ9 13. The cancer patients were also classified into Dukes’s classification (A, B, C) for colorectal cancer that gives doctors a guide to the risk, following surgery, of the cancer coming back or spreading to other parts of the body. An additional category (D) identified patients with disease that had not been completely resected. Perform an analysis of these data in which you identify the sources of variability and specify the degrees of freedom for each. Do these data provide sufficient evidence to indicate that, on the average, leucocyte counts differ among the five categories? Use Tukey’s procedure to test for significant differences between individual pairs of sample means. One important outcome variable was the rating of back pain at the beginning of the study. The researchers wanted to know if the treatment had essentially the same mean pain level at the start of the trial. The researchers used a visual analog scale from 0 to 10 cm where 10 indicated “worst pain possible. If warranted, use Tukey’s procedure to test for differences between individual pairs of sample means. Each of the 16 subjects had the tremor amplitude measured (in mm) under three conditions: holding a built-up spoon (108 grams), holding a weighted spoon (248 grams), and holding the built-up spoon while wearing a weighted wrist cuff (470 grams). Tremor Amplitude (mm) Subject Built-Up Spoon Weighted Spoon Built-Up Spoon þ Wrist Cuff 1. Norman, “A Randomized Controlled Trial of the Effects of Weights on Amplitude and Frequency of Postural Hand Tremor in People with Parkinson’s Disease,” Clinical Rehabilitation, 16 (2003), 481–492. The following table shows the alveolar cell count Â106 by treatment group for the ovalbumin-sensitized and nonsensitized guinea pigs. The researchers used the Masstricht Vital Exhaustion Questionnaire to assess vital exhaustion. One of the outcome variables of interest was the amplitude of the high- frequency spectral analysis of heart rate variability observed during an annual health checkup. Perform an analysis of variance on these data and test the three possible hypotheses. The effects of thermal pollution on Corbicula fluminea (Asiatic clams) at three different geographi- cal locations were analyzed by John Brooker (A-32). Sample data on clam shell length, width, and height are displayed in the following table. Determine if there is a significant difference in mean length, height, or width (measured in mm) of the clam shell at the three different locations by performing three analyses. Location 1 Location 2 Location 3 Length Width Height Length Width Height Length Width Height 7. The nine positions correspond to testing knee flexion angles of 1–10 , 11–20 , 21–30 , 31–40 , 41–50 ,51–60, 61–70 ,71–80, and 81–90. May weconclude, onthe basisof these data, that mean severity scoresdifferamongthethreepopulationsrepresentedinthestudy? Use Tukey’s procedure to test for significant differences among individual pairs of sample means. No dural ectasia: 18, 18, 20, 21, 23, 23, 24, 26, 26, 27, 28, 29, 29, 29, 30, 30, 30, 30, 32, 34, 34, 38 Mild dural ectasia: 10, 16, 22, 22, 23, 26, 28, 28, 28, 29, 29, 30, 31, 32, 32, 33, 33, 38, 39, 40, 47 Marked dural ectasia: 17, 24, 26, 27, 29, 30, 30, 33, 34, 35, 35, 36, 39 Source: Data provided courtesy of Reed E. The following table shows the arterial plasma epinephrine concentrations (nanograms per milliliter) found in 10 laboratory animals during three types of anesthesia: Animal Anesthesia 1 2 3 4 5 6 7 8 9 10 A. She studied 35 patients with a stroke lesion in the right hemisphere and 19 patients with a lesion on the left hemisphere. She also grouped lesion size as 2 ¼ “1-3 cm”; 3 ¼ “3-5 cm”; and 4 ¼ “5 cm or greater” One of the outcome variables was a measure of each patient’s total unawareness of their own limitations. Unawareness Score Lesion Size Left Right Group Hemisphere Hemisphere 2 13 11 10 10 13 9 11 10 9 9 10 10 9 8 10 8 3 8 10 10 12 10 14 11 10 8 4 13 13 9 14 10 19 13 10 10 14 15 9 Source: Data provided courtesy of 8 Adina Hartman-Maeir, Ph. A random sample of the records of single births was selected from each of four populations. The following table shows the aggression scores of 30 laboratory animals reared under three different conditions. One animal from each of 10 litters was randomly assigned to each of the three rearing conditions. Rearing Condition Extremely Moderately Not Litter Crowded Crowded Crowded 1 2 3 4 5 6 7 8 9 10 30 20 20 Do these data provide sufficient evidence to indicate that level of crowding has an effect on aggression? The following table shows the vital capacity measurements of 60 adult males classified by occupation and age group: Occupation Age Group A B C D 1 4. If an overall significant difference is found, determine which pairs of individual sample means are significantly different. In addition to studying the 12 type 2 diabetes subjects (group 1), Polyzogopoulou et al. The following data are the 12-month post- surgery fasting glucose levels for the three groups. For exercises 34 to 38 do the following: (a) Indicate which technique studied in this chapter (the completely randomized design, the randomized block design, the repeated measures design, or the factorial experiment) is appropriate. Johnston and Bowling (A-37) studied the ascorbic acid content (vitamin C) in several orange juice products.

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Te exomphalos has a sac lined by Clinical Features a translucent membrane that merges with the skin . It Te earliest manifestation is jaundice appearing round may be seen as a component of Beckwith syndrome about the 7th day after birth (even days and weeks later) . More than one- Jaundice , which is of obstructive type , is mild to begin with third of the cases have major cardiac anomaly warranting but progressively becomes severe . Gastroschisis is characterized by herniation of the Skin in due course becomes bronze , olive green in color . Intestinal atresia is associated in upto 20% Diagnosis of the cases , the most frequent association . Main diferential diagnosis is from neonatal hepatitis See Surgical treatment aims at reduction of the abdominal Chapter 25 (Fever Spectrum) . However, at times, no single viscera back to the abdominal cavity and closure of the or battery of tests may conclusively diferentiate the two. Due to exposure of the intestine, these Such cases should have operative cholangiogram before 8 infants are at risk of evaporative fuid losses and require weeks of age to demonstrate the patency or obliteration of aggressive fuid therapy and proper coverage of sac and bile ducts at a specialized center. Ventilation may be required for giant omphaloceles, which are managed with staged repair. Firstly, it may well result from intrauterine viral infection which, when severe enough, causes infammatory degeneration of the bile ducts and their replacement by fbrous tissue. Secondly, intrauterine ischemia of bile ducts has been incriminated as the cause of degeneration, disappearance and replacement with fbrous tissue of bile Fig. Tirdly, an unknown autoimmune reaction could the infant had gross obstructive jaundice and hemorrhages. Evidence 825 good number of patent ductules converge at porta hepatis of acute cholangitis in the form of pyrexia, right upper and when transected, discharge the pentup bile. In due course, ductal epithelium grows circumferentially and unites with the jejunal epithelium. Ultrasound is the best diagnostic tool for detecting both the intra and extrahepatic choledochal cysts. Recent advances include liver transplant if the Kasai’s Magnetic resonance cholangiopancreatography procedure fails to result in adequate drainage. Choledochal Cysts Treatment No longer considered rare, choledochal cysts are congenital Primary excision of the cyst and Roux-en-Y dilatation of the common bile duct that may end up in choledochojejunostomy is the treatment of choice. Postoperatively, Varieties rarely there is risk of sufering from complications such as anastomotic stricture, which leads to recurrent cholangitis. Type 1: Saccular or fusiform dilatation of the extrahepatic Cholecystitis (Calculus Type) biliary tree For details, See Chapter 25 (Fever Spectrum). Congenital Ureteropelvic Junction Obstruction Te most common types are the cylindrical and spherical cysts. Tis is the most frequent site of obstruction in the upper urinary tract and is the most common underlying Etiopathogenesis disorder leading to a diagnosis of antenatally detected Te etiopathogenesis remains speculative. It can be pancreatic junction with a long common excretory diagnosed antenatally by ultrasonography at 20 weeks or duct and a wide angle. Antenatal these cysts are: intervention is indicated in bilateral obstruction with Increased intraluminal pressure due to: equivocal function diagnosed early in intrauterine z Abnormal choledochus sphincter inferior life. Indications of postnatal surgery are symptomatic z Fibrosis of sphincter of Oddi obstruction, especially with compromised renal function z Post-inflammatory ductal stenosis and presence of caliectasis, decreasing function on follow- Weakness of the duct wall due to: up nuclear scans or thinning of cortex on ultrasonography. Tis is the most severe of the obstructive uropathies and can be diagnosed antenatally by ultrasonography. Clinical Features Anatomically, there is obstructing membrane of valve Te disease afects females four times more than males. In the infantile variety that accounts for 75% of the cases, Manifestations result from the severe bladder outfow presentation is with cholestatic jaundice (acholuric stools, obstruction that accrues. Surgical intervention is in the form of decompression dissolve the calculus or push it out. Rarely, if the child does not respond favorably to proper preventive measures should be instituted this procedure or cystoscopy is not feasible, vesicostomy accordingly. Renal Stone As a rule, renal stones are far less common in childhood Primary Bladder Stone Disease than in adults. Te occurrence of bladder stone despite the absence of Etiology any obstructive uropathy, local predisposing cause in the Te causes of urolithiasis in pediatric age group are: bladder itself or infection among children tropical regions Metabolic: has aroused considerable interest. Besides India, it has z Idiopathic calcium oxalate stones because of been endemic in North Africa, Syria, Saudi Arabia, Iran, absorptive or renal hyperoxaluria, hyperuricosuria, Burma, Pakistan, Tailand, Afghanistan and Indonesia. In hypocitraturia or most commonly hypercalciuria India, the disease is common in Northeast states, Andhra z Primary hyperoxaluria Pradesh and Rajasthan followed by Delhi, Uttar Pradesh, z Orotic aciduria Haryana, Punjab and Jammu and Kashmir. A large z Enteric urolithiasis majority of the patients are under 10 years of age. Males z Hypercalcemic states—hyperparathyroidism and are afected more often than females. Renal disorders: z Cystinuria Etiology z Renal tubular acidosis Te exact etiology of primary bladder stone disease is Secondary: not clear. High oxalate diet also contributes to this z Post urinary diversion procedures condition. It has been postulated that recurrent attacks Endemic bladder and renal stone disease. Likewise, recurrent Tese include recurrent infections, renal colic (colicky febrile illnesses have also been incriminated in its etiology. Te signs and symptoms of the underlying protein results in high urinary ammonium concentrations. In an infant the features are Coupled with high urates, this leads to ammonium urate often nonspecifc. Diagnosis Clinical Features It is imperative to conduct a full metabolic work-up to rule Manifestations include dribbling of urine, painful out the above-mentioned causes otherwise a recurrence micturition (pain over tip of penis is typical) and is likely. It is equally important some children, genital handling, masturbation and rectal to measure the pH and to do the rest of the routine exam prolapse may also be noticed. Te X-ray and ultrasonography of abdomen confrm the stones are composed of mainly urates and oxalates. For planning of therapy, an intravenous Surgical removal is the sole treatment of bladder stone. Etiology 827 Te etiologic factors include leukemias, sickle-cell disease and perineal trauma. Treatment of leukemia with chemotherapy and local irradiation of sickle cell disease with rapid hypertransfusion using packed red cells, of perineal trauma with surgical drainage of afected areas and creation of vascular shunt between corpus spongiosum and corpora cavernosa so as to produce detumescence leads to of resolution of priapism. Tight External Urethral Meatus (Meatal Stenosis) A tight meatus with thin stream and, perhaps, some Fig. Note the obvious swelling in the left inguinal dysuria, on micturition may follow a healed meatal region on crying. In view of the potential risk of strangulation, it must be trauma, infammation or ulcer, or an inappropriately timed operated as early as possible. It is is unretractable at birth (physiologic phimosis), but in helpful, but not really diagnostic of inguinal hernia. Inguinal hernia requires operative treatment as early By adolescent, only 1% have phimosis. Phimosis may be as possible in view of high incidence of obstruction and congenital or secondary to infammatory condition(s) of strangulation. Standard treatment for pathologic or true phimosis is and constipation (obstructed or strangulated hernia). Alternatively, betamethasone cream may be applied Hydrocele to the narrowed preputial skin twice daily for 4 weeks. After 2 weeks, the foreskin becomes soft and elastic and Te term, hydrocele, implies presence of peritoneal fuid is retracted gently and gradually in increments. Noncommunicating hydrocele is quite common in Paraphimosismeans that once the prepuce (phimotic) newborns and infants. It disappears spontaneously is retracted behind coronal sulcus, it cannot be reduced. Te scrotal swelling is nontender and well can be attained by application of lubricants under cover of transilluminated. Communicating hydrocele is characterized by rapid Hypospadias and Epispadias change in size in the subsequent months. Tere is a Te term, hypospadias, denotes abnormal placement of communication with the peritoneal cavity through the the external urethral meatus on the ventral aspect of the patent processus vaginalis. Tese cases need full evaluation for ambiguous Surgical intervention is indicated only when hydrocele sex and surgery. Te operation involves ligation and division of patent processus vaginalis Ambiguous Genitalia through a small inguinal incision. If It results from persistence of the patency of processus cryptorchidism is left as such, diminished spermatogenesis vaginal is accompanying the spermatic cord. In some cases, associated enlargement Infammation of epididymis (epididymitis) testes (orchitis) of the tongue may occur. In case of mumps, orchitis usually follows parotitis Spontaneous regression does not occur. A large unilocular cyst tender and swollen with red and edematous adjacent may respond to intralesional sclerotherapy in the form of skin. It is a smooth rounded midline neck swelling which is Acute Scrotum connected by a tract to the base of the tongue, representing the persistence of the thyroglossal tract postnatally. It Acute scrotal swelling may result from epididymo-orchitis, is likely to get repeatedly infected and burst. It should torsion of testis or its appendages, testicular trauma or be diferentiated from submental or pretracheal lymph idiopathic scrotal edema. It is of paramount importance nodes and ectopic thyroid gland, which, unlike the cyst, to diferentiate between testicular torsion and the other is always present at birth. Treatment is immediate of the body of the hyoid bone is a part and parcel of this surgical intervention, correcting the torsion and fxing the procedure otherwise recurrence as likely. Cystic Hygroma Brachial Sinus and Fistula (Lymphangioma) Branchial sinus is a discharging sinus at the anterior Tese are massive, nontender, unilocular or multicystic border of sternocleidomastoid (the junction of its middle tumors with semitransparent walls and thinning of the and lower thirds) and extends to external auditory canal overlying skin. Treatment is careful excision often at birth and occur in the head and neck region as the tract passes in between the external and internal (Figs 46. It is also called lymphangiomas, these tumors are capable of causing complications by their extension into the thorax and compression. Tere are no infammatory signs, z Neurogenic: Posterior fossa (cerebellar) or spinal cord tumor in but the child has torticollis due to muscle shortening. Abscess is a common pediatric surgery problem and signifes Treatment consists of stretching the afected muscle pus under pressure. Clinically, there is painful swelling with to the overcorrected position by gentle manipulation redness of overlying skin, fever and fuctuation on palpation. If response to conservative treatment Abscess can occur virtually in any body part. Examples are breast abscess, abdominal wall abscess, psoas abscess, liver continues to be discouraging by 6–12 months of age, abscess, etc. Treatment entails surgical drainage and appro- surgical lengthening and division of the sternal portion of priate antibiotics. As the most common organisms are Gram- the muscle or from mastoid process at its origin followed positive cocci (Staphylococcus and Streptococcus penicil- by exercise program should be carried out. Else, the infant lin group of drugs which also cover the penicillin-resistant may develop asymmetry of the skull and face, cervicodorsal strains, i. An intestinal mucosa-lined patch in the umbilicus presenting with discharge from umbilicus is: A. Phimosis at birth is usually physiologic, disappearing by 3 years of age in 90% cases 4. The best test for determining the level of defect in anorectal malformation is: A. B 830 Clinical Problem-solving Review 1 A newborn, immediately after birth, develops respiratory distress with cyanosis, chest retractions and gasping. There is nothing suggestive of an intestinal infection and there is no abdominal discomfort. The frst and foremost aim is to stabilize the cardiorespiratory system by decreasing the pulmonary arterial pressure. Laparotomy for reduction of viscera and repair of defect in thew diaphragm follows stabilization. Meckel’s diverticulum which results from persistence of embryologic vitellointestinal duct. Bleeding in this condition occurs due to a band going up to umbilicus or perforation secondary to ulceration from ectopic gastric mucosa. After the high index of suspicion, confrmation of diagnosis is by a barium meal study or yet better, a technectium-99m- labeled radionuclide scan. Treat- ment consists of conservative measures such as arch sup- Phocomelia is a reduction deformity (congenital port, shoe modifcation and exercise. If this treatment fails, amputation) in which there is gross reduction in the orthopedic intervention in the form of removal of calcaneus proximal part of the extremity so that distal part seems to or, after age 10 years, arthrodesis. Treatment in most cases T e hand is deviated laterally because of partial or total revolves around amputation and orthotic rehabilitation. Orthopedic treat- In this condition, the thumb cannot be straightened since ment in the form of corrective manipulation with adhesive it is locked in fexion because of a nodular swelling of the tapes, splints or casts and wedging is helpful, provided it is long fexor tendon at the base of the thumb. Clinically, fatfoot is recognized when the An extra fnger/toe, usually close to the metacarpophalan- arch touches the ground on weight bearing or is close to geal joint of the little fnger/5th toe or the thumb, may occur the ground.

As for previously immunized subjects , a recall dose Te peak incidence of typhoid occurs in summer of toxoid sufces . Conduction of deliveries , both in and and rainy season when fy population shows enormous outside the hospital , under clean and aseptic conditions increase . Contrary to the popular belief and West-oriented and application of clean dressing during healing of cord teaching , typhoid is certainly common in infants and are also important . A recent survey in a slum-population of Delhi revealed an overall Prognosis incidence of 9 . No doubt , the clinical up with cerebral palsy , paralysis, mental retardation, and picture in pediatric typhoid is remarkably diferent from behavioral problems as sequelae of apnea and anoxia what is often seen in the grown-ups. A survivor chronic carriers happen to be the major source of spread from tetanus needs active immunization since tetanus does of infection. Unlike adults, who show insidious onset with An acute bacterial infection, characterized by constitu- step-ladder rise in temperature, typhoid in children often tional symptoms like prolonged pyrexia, prostration and manifests suddenly. It does not cause Te manifestations are rapid rise of temperature, lifelong or even sufciently prolonged immunity. Te paradoxical relationship of low pulse rate and high pyrexia is not Etiopathogenesis common in children. Te disease is caused by Salmonella* typhi and Salmonella Some cloudiness of consciousness (this is what the paratyphi A, B and C** lead to a typhoid-like illness, the so- term, typhoid, denotes) is almost always present. Bradycardia, perhaps true of most other tropical and subtropical regions, an important sign in adults, is not a common fnding in especially where standards of sanitation and hygiene are pediatric patients. Transmission is by contaminated food, unboiled A rash (macular red rose spot) is said to appear about milk, vegetables or water. Housefy plays a signifcant role the ffth day on the front and the back of the trunk. In * Besides enteric fever, Salmonella may cause (1) septicemia, (2) enteritis/dysentery, (3) meningitis, (4) pneumonia/bronchitis, (5) osteomyelitis, (6) appendicitis and (7) peritonitis. Investigations 369 Eosinopenia or complete absence of eosinophils is a reliable fnding. Leukopenia with relative lymphocy- tosis, described as an important feature of typhoid, is most often absent. Tis is perhaps due to the fact that the patients generally report fairly late, particularly in developing countries. In our conditions of endemicity of typhoid, a ‘O’ antibody titer of 1 in 160 or more in the second week of symptoms is suggestive of the disease. In order to exclude the anamnestic responses, it is advisable to perform a modifed Widal test along with a conventional Widal test. Note the splenomegaly detected in the turning to be positive in the second week are around third week. Complications In typhoid of infancy and early childhood, clinical pro- Unlike adults, children with typhoid fever have far less inci- fle usually includes fever with or without diarrhea, dence of abdominal complications. Anemia may lems, especially those of respiratory and nervous system, be secondary to blood loss or hemolysis from auto are, however, more frequently encountered (Box 19. Even neonates may develop Treatment the disease as a result of vertical transmission. Accompanying manifestations include seizures, ramphenicol, amoxycillin, ampicillin, cotrimoxazole stand jaundice, hepatomegaly, anorexia and weight loss. Onset with acute abdomen and vomiting may sug- liver, cholecystitis and urinary tract infection. If meningeal signs are z Neurologic: Encephalopathy, meningitis, myelitis, Guillain-Barré there, meningitis must be ruled out. Clinical z Hematologic: Hemolytic anemia, bone marrow depression, Te most important is the clinical suspicion. Surgical inter- complicated cases vention may be needed for intestinal perforation. Hydrotherapy Uncomplicated typhoid (tepid sponging) is the more favored method of z Fully sensitive Chloramphenicol, amoxycillin treating hyperpyrexia of typhoid fever. For eradication of infection in chronic carriers, high z Multidrug resistant Cefxime, fuoroquinolones dose ampicillin (preferably along with probenecid), z Quinolone resistant Azithromycin, ceftriaxone given for 4–6 weeks, is recommended. Cholecystectomy is indicated in case of z Fully sensitive Ceftriaxone failure of drug therapy in chronic gallbladder infection. Oral cefxime has been found to be an efective switch Public health measures constitute the most important or step-down therapy, i. Other agents z There should be well-organized efforts and plan- which are good for switch therapy include quinolones and ning to improve sanitary conditions and personal, coamoxiclav. Administration of steroids is recommended groups, community, food and kitchen hygiene. Tese include: Detection and treatment of carriers is another important Isolation of the patient. Prognosis Attention to maintenance of adequate fuid and dietary With adequate treatment, prognosis is generally good. A nourishing light fuid or semisolid diet is advis- For some unknown reason, it has a more favorable able during the frst few days. Rigid dietary regimens are prognosis in children though, in infants, it is rather not no longer recommended. Vitamin and hematinic supplements are often needed Factors adversely afecting the prognosis and causing in most of the patients. Diagnosis 371 Tis is a remarkable decline compared to the preinde- Most useful diagnostic test early in disease is brucella pendence fgures of 25–50%. Comple-ment- Relapse is said to occur if the individual again develops fxation titer of 1:16 or higher is diagnostic later in the course of manifestations of the disease after about 1–2 weeks the disease. Defnitive diagnosis is by isolation of the organism of stoppage of antibiotic therapy for typhoid fever. Treatment Chronic carrier state is said to occur if the individual Doxycycline as such or in combination with streptomy- excretesS. Such subjects have chronic gallbladder 3-week course of doxycycline in combination with cot- infection or chronic urinary carriage, the latter being rimoxazole as also amoxycillin-gentamicin combination rare, except in patients with schistosomiasis. Some authorities recommend giving typhoid vaccine Prognosis (preferably whole cell killed) after full recovery from typhoid since one attack does not provide solid or long-lasting Prognosis following specifc chemotherapy is excellent. It is argued that the child with Tuberculosis, caused by Mycobacterium tuberculosis, is typhoid is likely to go back to the same environment with the most common chronic infectious disease globally. Te topic is dealt with in details It is also called undulant fever, Mediterranean fever or Goat in See Chapter 26 (Pediatric Pulmonology). In the relatively Etiopathogenesis rare acquired syphilis, infection is acquired through Brucellosis is caused by Gram-negative organism, Brucella, kissing, by sexual contact or through infected nipples. Following entry into the body, the syphilis is heading for elimination from India. In sex organisms are phagocytized by leukocytes and monocytes workers, it is around 3–4%. For details on congenital and spread throughout the reticuloendothelial system syphilis, turn to Chapter 23 (Intrauterine Infections). IgM antibodies develop early followed by IgG Defnition antibodies which eventually dominate. Granuloma formation, especially in liver, spleen, Leptospirosis is a zoonotic (spirochete) infection, the lymph nodes and bone marrow constitutes hallmark of causative bacteria fnding entry into human through a the disease. Granulomatous involvement of gallbladder, breach (abrasions and cuts) in skin or mucus membrane testes, heart, brain, kidney, bone and skin may also occur. Etiopathogenesis Clinical Features Te etiologic bacteria is Leptospira, a spirochere (Fig. Primarily, Onset is usually insidious with prodromal symptoms Leptospira damages the endothelial lining of blood vessels, such as weakness, weight loss, exhaustion, anorexia, resulting in ischemic insult to liver, kidneys, meninges and constipation, headache, muscle pains, etc. After an incubation period of 7–12 days, septicemic phase Hepatosplenomegaly and cervical and axillary lym- sets in. During this phase of 2–7 days, organisms can be phadenopathy are prominent fndings. Tis is followed by an immune phase (of 372 of 4–5 years though the child may have been infected much earlier. Microscopic appearance of the causative occupy a phylogenetical position between viruses and bacteria, Leptospira, which are long, thin, spiral-shaped motile spirochete. Over the years, scrub typhus cases from various parts of India too are on the increase. Leptospirosis may be asymptomatic Spotted fever group (subclinical) or symptomatic. Indian spotted fever) Mild asymptomatic disease is anicteric whereas severe Transitional group disease is icteric (Weil’s syndrome). Typhus group z Rickettsia typhi (Murine typhus) Differential Diagnosis z Rickettsia prowazekii (louse-borne or epidemic It is mainly from febrile illnesses such as dengue, malaria, typhus) (Fig. Hantavirus infections Orientia tsutsugamushi (Scrub typhus) may also cause confusion in the diagnosis. Diagnosis Diagnosis is confrmed by serology (microscopic aggluti- Transmission nation test) which is only infrequently available. Arthropods: Ectoparasites like ticks, mites, lice and feas Dark-feld examination of blood—not quite specifc Animal reservoirs: Rodents, dogs and cats. From lymph nodes, it As soon as the diagnosis is suspected, treatment with paren- tends to spread systematically. Te vasculature of the teral penicillin G (alternatively, tetracycline, doxycycline, pro- organs at the endothelial level gets invaded. Prevention Clinical Features It is in the form of rodent control measures, avoidance of contaminated water and soil, and once a week doxycycline Incubation period is 2–14 days. Unlike Scrub typhus may present with fuid in the third space adults, early manifestations of leprosy in childhood are (ascites, pleural efusion) or pneumonia. Generally, it is not diagnosed until the age week of illness, neurological manifestations may occur. Diagnosis Complications High index of suspicion, especially in case scenarios where Acute pulmonary edema common conditions do not appear to be the cause of fever Pneumonia is the gateway to diagnosis. Meningoencephalitis/encephalopathy Investigative fndings are nonspecifc in the form of Myocarditis leucocytosis or leucopenia, low hemoglobin, throm- Septic shock bocytopenia, hyponatremia and high liver enzymes Renal failure (aminotransferases). Since diagnosis in a large majority of cases is clinical, Leaving the clinically suspected case untreated for a empirical therapy is strongly recommended. Differential Diagnosis Alternatively, tetracycline, chloramphenicol, azithromycin, Exanthematous fever (measles, infectious mononu- roxithromycin or rifampicin may be employed. All of the following observations about bacterial infections are correct, except: A. Toxic shock syndrome may be caused by Staphylococcus aureus and Streptococcus pneumonia B. Meningococcal vaccine for normal children as a part of routine vaccination is not recommended D. During convalescence from diphtheria, if Schick test is positive, diphtheria toxoid need not be given 2. For fully sensitive and quinolone resistant, severe/complicated typhoid fever, the drug of choice is ceftriaxone B. Both maternal and neonatal tetanus are in the last stage of elimination from India Answers 1. Dengue and malaria tests as also Widal (done on 5th day of illness) and urine examination negative. What should be the most logical diagnosis in view of the clinical fndings and results of investigation? Chloramphenicol, once the drug of frst choice for typhoid fever, remained out of use over many years on account of resistant strains. Review 2 An 18-month sick-looking toddler presents with skin lesions which show separation of the areas of superfcial epidermis leaving behind denuded areas of skin on a sheer gentle touch and fever. Though Widal test is negative, it becomes meaningless since it was done on 5th day of illness when it is expected to be negative even in typhoid fever. Today, chloramphenicol remains the drug of choice in fully sensitive uncomplicated cases of typhoid fever. T ese infections, if not appropriately treated, may turn out Prevention to be a major cause of morbidity and mortality. Pulmonary manifestations include cough, chest pain, Superfcial infections manifest in the form of oral thrush, weight loss and fever. Hemolytic anemia and hepatosple- manifests, just like bacterial infections, as: nomegaly may be present. Sepsis Meningitis Diagnosis Endocarditis Radiological features: Difuse infltration with hilar Septic arthritis lymphadenopathy Osteomyelitis. Serological assay for immunoglobulin G (IgG) and IgM Serological testing for cryptococcal polysaccharide Diagnosis antigen by latex agglutination High index of suspicion clinches the clinical diagnosis. Clinical and radiological response is necessary for cessation of Te most frequent etiological species are Aspergillus fumigatus followed by A. Etiology Clinical Features Mucorales are responsible for mucormycosis, the third most Manifestations include signs and symptoms in relation common invasive fungal infection. Based on anatomic location, Invasive manifestations are over and above the mucormycosis is classifed in six forms: noninvasive manifestations such as sinusitis, 1. Sporadic patients mucormycosis is a life-threatening condition, almost always Specifc laboratory techniques, especially: associated with certain risk factors, mainly neutropenia and z Biopsy for histopathological identification of prolonged acidosis, either diabetic or renal origin. Neurological presentation, as and when it occurs, is in Management the form of meningoencephalitis with or without focal Antifungal therapy using amphotericin B intravenously neurological defcits.

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