Gastroesophageal reflux in infants.
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Biomedical subjects
Publications and source records attributed to M K Farrell.
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In a one-year prospective study we assessed the incidence of Reye's syndrome in children presenting with the acute onset of vomiting after a prodromal upper-respiratory-tract infection or varicella, and with serum alanine or aspartate aminotransferase levels at least three times higher than normal, and a paucity of neurologic findings. Of 25 patients meeting the above criteria, 19 had liver biopsies yielding adequate tissue for diagnostic purposes. Biopsy specimens from 14 of these 19 patients (74 per cent) were diagnostic of Reye's syndrome, according to rigorous light-microscopical, histochemical, and ultrastructural criteria. None of the biopsy specimens contained evidence of other acute pathologic processes, including hepatitis. A wide spectrum of mitochondrial alterations existed at the ultrastructural level, ranging from mild to severe lesions that were indistinguishable from those seen in comatose patients with Reye's syndrome. Our findings suggest that the clinical complex of vomiting, hepatic dysfunction, and minimal neurologic impairment after varicella or an upper-respiratory-tract infection usually represents Reye's syndrome. This syndrome occurs more frequently than previously recognized.
To characterize differences in intestinal absorption of fat-soluble vitamins during cholestasis, intestinal absorption of vitamin E was compared with that of 25-hydroxyvitamin D in eight infants and young children with prolonged neonatal cholestasis. Oral tolerance tests were performed using 100 IU/kg/dose dl-alpha-tocopherol and 10 micrograms/kg/dose 25-hydroxyvitamin D. Mean vitamin E absorption was only 1.0% to 1.9% of that of control children, whereas 25-hydroxyvitamin D absorption was 22.5% to 25.1% of that of controls. Although intestinal absorption of both vitamins is impaired during cholestasis, the severity of vitamin E malabsorption far exceeds that of 25-hydroxyvitamin D.
Antibiotic therapy for children without foci of infection and at risk for bacteremia is controversial. A prospective randomized clinical trial was conducted using expectant antibiotic therapy in children at risk for bacteremia. A total of 96 children (aged 6 to 24 months) with temperature of more than 40 degrees C, no identifiable source of infection, and a leukocyte count greater than or equal to 15,000/microL and/or sedimentation rate greater than or equal to 30 were enrolled. The following tests were performed on all children: blood culture, chest roentgenogram, urinalysis, and urine culture. A lumbar puncture was performed if a child was 12 months or less. Patients were randomized to receive either no antibiotic therapy or Bicillin C-R, 50,000 U/kg intramuscularly, followed by penicillin V, 100 mg/kg/d, orally four times a day for three days. Patients were examined at 24 and 72 hours. Fifty patients were treated expectantly and 46 received no antimicrobial therapy. Ten of the 96 patients were bacteremic (nine had Streptococcus pneumoniae, one had Haemophilus influenzae). Four of the five children treated for bacteremia showed improvement at the first follow-up visit (afebrile and no obvious focus of infection). The five untreated patients showed no improvement; four patients developed focal infections (two had meningitis, two had otitis media) (P less than or equal to .05, Fisher exact test). No complications of expectant therapy were detected. Thus, expectant antibiotic therapy for children who have no obvious source of infection and who meet these criteria associated with occult bacteremia is warranted.
III infants and children need zinc replacement in total parenteral nutrition solutions, but assessment of these needs and total body zinc status is difficult. Seven infants with severe diarrhea initially given 80 to 100 micrograms/kg/day of elemental zinc developed systemic zinc deficiency as indicated by an acrodermatitis-like skin rash and low serum alkaline phosphatase. Serum zinc levels were borderline low only in conjunction with hypoalbuminemia. Daily urinary zinc excretion was normal. With increased zinc supplementation of 200 to 300 micrograms/kg/day, the rash healed and serum alkaline phosphatase rose to normal levels for age. The activity of the metalloenzyme alkaline phosphatase accurately reflects total body zinc status in infants. With diarrheal illness, infants, need high doses zinc supplementation to replace considerable stool losses.
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Periodic breathing (PB) during sleep was investigated in two groups of full-term infants with histories of apnea that were terminated by resuscitation. One group of infants had been reported to be asleep whereas the other group had been reported to be awake when apnea was noted. Electrophysiologic sleep recordings were made after the apneic incident. The infants with histories of prolonged apnea while asleep exhibited more PB during recorded sleep than infants with histories of apnea while awake. Increased PB during sleep in full-term infants, therefore, may not be associated with all prolonged apneic episodes in infants but may be specifically associated with those episodes that occur during sleep.
The temporal relationship between apnea and gastroesophageal reflux was examined in 14 infants with abnormal GER scores and histories of prolonged apnea. Simultaneous polysomnographic and intraesophageal pH recordings were performed for each infant. GER episodes were compared to control segments of the recording (without GER) for frequency and type of apnea. Apnea was equally likely to occur during the control segments as during the GER episodes. Brief obstructive apneic episodes were more common during the onset of GER episodes than the onset of control segments. GER duration appeared prolonged during sleep. GER and apnea were not temporally related in the majority of instances, and may be two manifestations of a more general developmental delay.
Serum levels of the primary bile acids cholic and chenodeoxycholic acid are transiently elevated in normal neonates and infants; this represents a state of "physiologic cholestasis." In this study we determined, using specific radioimmunoassay, the concentration of a secondary bile acid, sulfated lithocholate, in serum obtained from healthy infants and from those with various hepatobiliary diseases. The serum levels of sulfated lithocholate were low in 69 neonates (less than 5 days of age: mean +/- SEM = 0.45 +/- 0.05 mumoles/L) and in 78 normal infants (less than one year of age: 0.49 +/- 0.02); there was no postprandial rise. These values were similar to those seen in 95 older children (0.56 +/- 0.03) and in maternal (0.49 +/- 0.04) and cord blood (0.44 +/- 0.03) of the neonates. In contrast, in patients with neonatal cholestasis of any nature there was a consistent marked rise in serum concentrations of sulfated lithocholate (mean = 4.46 +/- 0.39, P less than 0.001). In infants monitored during the course of parenteral nutrition, elevated values of sulfated lithocholate often occurred in the presence of normal results of other liver function tests. Serum sulfated lithocholate concentration is an accurate index of neonatal hepatobiliary disease; the sensitivity and specificity of this test remain to be further defined.
Continuous enteral feeding is utilized for nutritional support and specific therapy for several pediatric diseases, including protracted infantile diarrhea. Its effects on the enterohepatic circulation of bile acids were studied in a boy during continuous intragastric feeding of a high fat diet at age 42 months and after recovery while on bolus feedings at age 51 months. Cholic acid kinetics measured by the isotopic dilution technique using cholic-COOH-14C acid and meal stimulated intraluminal bile acid concentrations were measured. Cholic acid pool size was unaltered (1294 mg/m(2)) during continuous feeding compared to 999 mg/m(2) during bolus feeds and 1072 plus or minus 243 mg/m(2) (mean plus or minus SE) in nine control children. However, the cholic acid fractional turnover rate was increased 3-fold (0.912 days(-1)) during continuous feeds compared to 0.309 days(-1) during bolus feeding and 0.365 plus or minus 0.163 in controls. Similarly, synthesis rate was increased 3-4 fold during continuous feeds (1180 mg/m(2)/day) compared to controls (363 plus or minus 193 mg/m(2)/day) and the patient during bolus feeding (309 mg/m(2)/day). The intraluminal bile salt concentration was apparently reduced both during treatment (3.86 mM) and when bolus fed (3.85 mM) but were significantly different from controls (7.12 plus or minus 1.74 mM). During continuous enteral feeding with a high fat diet, effective homeostatic mechanisms in the enterohepatic circulation of bile salts ensured intraluminal bile salt concentrations adequate for normal fat solubilization and, consequently, normal fat absorption.
Forty-six children less than 12 years of age with gonorrhea were studied over a 4 1/2-year period. The investigation was conducted by a multidisciplinary team including physicians, social workers, and health department representatives. Extensive interviewing and routine culturing of contacts eventually identified the source of gonorrhea in 38/46 (83%) children. Males, both adult and preadolescent, were implicated as the source of gonorrhea almost twice as often as the child's mother. Nineteen children were victims of sexual assault, but only four of them had a hymenal orifice larger than one fingerbreadth. Compliance, both in pursuing the history and obtaining cultures of contacts, was significantly increased by admission to the hospital. A Gram stain and culture for gonorrhea should be done in all children presenting with vaginal discharge regardless of history. Hospitalization of children with suspected gonorrhea greatly facilitates the contact identification.
A distinctive myopathy was observed in 24 children following influenza B infection. The abrupt onset of severe muscle pain and difficulty in walking began as the respiratory symptoms were waning. The lower extremities, particularly the gastrocnemius and soleus muscles, were involved preferentially. Nasopharyngeal cultures were positive for influenza B Hong Kong in 18 of these patients. Serum creatine phosphokinase levels were significantly elevated (mean 55.2 units) when compared to controls and nine patients with Reye syndrome. The cardiac muscle isoenzyme was detected in the serum of 17 myopathy patients. Serum glutamic oxaloacetic transaminase, but not serum glutamic pyruvic transaminase, was elevated compared to controls (P less than 0.01) but less (P less than 0.001) than the patients with Reye syndrome. Twelve patients underwent muscle biopsy; segmental rhabdomyolysis without inflammation was detected in nine patients. Myopathy is a complication of influenza infection that can be diagnosed by clinical, biochemical, and virologic examination.
Hyperalimentation is a feeding technique in which all essential nutrients are infused intravenously to sustain patients who cannot eat. Although no panacea for anorexia nervosa, hyperalimentation can provide calories for intractable, malnourished patients. The authors describe the psychiatric and hyperalimentation treatment for four severely anorectic patients who had lost up to 44% of their body weight before entering the study. With treatment their percentage of ideal weight rose from a mean of 59% to a mean of 81% during hospitalization, and to a mean of 94% on outpatient follow-up of 5--16 months. The authors discuss the indications, limitations, and need for interdisciplinary collaboration in this treatment.
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The adequacy of low dose vitamin D (25 IU/dl) parenteral nutrition (PN) solution was studied in 18 infants. All infants had surgical indications for PN. The birth weights were 2810 +/- 135 g and gestational ages 37.4 +/- 0.5 wk (mean +/- SEM). Duration of study ranged from 5 to 175 days. Thirteen infants were studied for up to 6 weeks and five infants for 71 to 175 days. Results showed that studied infants maintained growth along normal percentiles for weight, length, and head circumference. Vitamin D status as indicated by serum 25 hydroxyvitamin D (25 OHD) rose from 15 +/- 1.9 ng/ml to 26 +/- 2.8 ng/ml, mean +/- SEM (p less than 0.001) after 9 days, and remained normal up to 6 months. Five infants with biochemical liver dysfunction also had normal serum 25 OHD concentrations, indicating the hepatic 25 hydroxylation process was not severely impaired. Serum total and ionized calcium, phosphorus, and vitamin D-binding protein concentrations were normal. Serum magnesium was mildly elevated in five infants (2.6 to 3 mg/dl) on one occasion and resolved spontaneously. Serum alkaline phosphatase (AP) concentrations rose above baseline values in 12 of 17 infants, but remained within normal range (less than 400 IU/liter at 30 degrees C). Another infant with markedly elevated AP values died from liver dysfunction. Radiographs of the forearms were normal except for marked demineralization in one infant in spite of normal 25 OHD concentrations. We conclude that 25 IU vitamin D/dl of nutrient infusate is adequate to maintain normal vitamin D status, as indicated by normal serum 25 OHD concentrations in infants receiving PN for as long as 6 months.
Calf muscle samples were obtained from 12 children with transient incapacitating myalgia and proved infection of the upper respiratory tract with influenza virus, type B. In all except one, light microscopy revealed isolated segmental muscle fiber degeneration and necrosis without frank myositis. Ultrastructural studies revealed that in zones of segmental necrosis, the sarcolemma was lysed but the basement membrane was intact. Focal degenerative changes included myofibrillar disarray with disruption/loss of the sarcoplasmic reticulum, glycogen depletion accompanied by mitochondriopathy, subsarcolemmal mitochondrial aggregates, activation of satellite cells, and focal filopodial transformation of the sarcolemma. The primary event in the pathogenesis of focal muscle fiber necrosis is likely to be biochemical and was not elucidated, but the focal sarcolemmal and T-tubule changes and mitochondriopathy suggest that destabilization of cell membranes may play a critical role. Sarcolemmal filopodia may be a marker for a specific type of membrane injury, but we were unable to establish that influenza virus has a direct role in its genesis.