Dana E. Johnson

Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers

Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration.

Medical Evaluation of Internationally Adopted Children

BACKGROUNDnDespite many reports of medical illness in children adopted from abroad, there are currently no accepted guidelines for medical evaluation of this population.nnnMETHODSnTwo hundred ninety-three children adopted from 15 countries (mean age, 14.0 months; 55 percent girls) were evaluated by history taking, physical examination, and screening tests for hepatitis B virus (HBV), human immunodeficiency virus type 1, tuberculin reactivity, intestinal parasites, syphilis, excretion of cytomegalovirus, renal disease, and anemia. All but four were seen within one month of their arrival in the United States.nnnRESULTSnFifty-seven percent of the children (168 of 293) were found to have at least one important medical condition. Eighty-one percent of the diagnoses were established by screening test, rather than by history taking or physical examination. Infectious diseases made up the majority of the medical conditions (73 percent). Serologic testing for hepatitis B surface antigen was positive in 5 percent of the children. Characteristics associated with the acquisition of HBV infection included arrival within the first three years of the study (P = 0.017), Asian origin (P = 0.011), and receipt of a blood transfusion abroad (P = 0.008). Ten children (3 percent) had positive Mantoux skin tests, and four of these had active pulmonary tuberculosis. Tuberculin reactivity was significantly associated with older age (P less than 0.001) and lower weight (P = 0.037). Intestinal parasites were isolated from 14 percent of the international adoptees. Non-Korean adoptees were 16 times more likely to be harboring at least one intestinal parasite than were Korean adoptees (P = 0.005).nnnCONCLUSIONSnDirected screening tests should be a routine component of the medical evaluation of all children adopted from abroad, regardless of age, sex, or country of origin.

Observations concerning the microbial etiology of acute salpingitis.

Abstract OBJECTIVES : The specific aims of this study were (1) to describe the microbiologic characteristics of patients with acute salpingitis and (2) to determine the incidence of bacterial vaginosis in patients with acute salpingitis and whether bacterial vaginosis microorganisms were common upper-genital-tract isolates in these patients. STUDY DESIGN: Women with pelvic inflammatory disease underwent laparoscopy to confirm the diagnosis of acute salpingitis and for culture of the fallopian tubes and cul-de-sac. Endometrial and minute fimbrial biopsies were performed, and specimens were evaluated for evidence of inflammation. Bacterial vaginosis was diagnosed by vaginal Gram stain. RESULTS : Eighty-four patients had visually confirmed acute salpingitis. Neisseria gonorrhoeae or Chlamydia trachomatis was isolated from 65 (77.4%) patients. Vaginal microorganisms were isolated from the endometrium in 16 (31.4%) of 51 cases and from the cul-de-sac in 12 (14.3%) of 84 cases. Bacterial vaginosis was present in 61.8% of patients with acute salpingitis, and 100% of anaerobes isolated from the upper genital tract of patients with acute salpingitis were bacterial vaginosis micororganisms. These anaerobes were isolated from the upper genital tract in the absence of a concurrent gonococcal, chlamydial, or Haemophilus influenzae infection in only two cases. CONCLUSIONS : The initiation of acute salpingitis is predominantly due to the ascending spread of sexually transmitted microorganisms. Bacterial vaginosis is a common concurrent disorder of women with acute salpingitis, and bacterial vaginosis microorganisms are commonly isolated from the upper genital tracts of patients with pelvic inflammatory disease. (AM J OBSTET GYNECOL 1994; 170:1008-17.)

Endocrine pancreas in cystic fibrosis: An immunohistochemical study

The pancreases of 17 patients who had cystic fibrosis with and without diabetes mellitus were evaluated at autopsy by routine staining and immunohistochemical methods for insulin, glucagon, somatostatin, and pancreatic polypeptide. Qualitative assessment of the number of islets of Langerhans and the degrees of exocrine pancreatic atrophy, fibrosis, and fat replacement was made for each pancreas. Quantitative assessment of islet composition was performed in 15 of the 17 based on the immunochemical reactivity of each cell type. Nondiabetic patients with cystic fibrosis in the latter part of the first decade of life have classic fibrocystic changes of the pancreas, with some persisting exocrine tissue, islets that appear normal, and prominent nesidioblastosis. The latter process may protect these patients from glucose intolerance. Young adult diabetic patients with cystic fibrosis have total loss of exocrine pancreas with fat replacement, lack of nesidioblastosis, a qualitative decrease in the number of islets, fibrosis of and amyloid deposits in islets, decreased numbers of insulin-containing cells in each islet, and atrophy of islet cells, probably resulting from progressive ischemia. Although the potential exists for an increasing incidence of diabetes mellitus in patients with cystic fibrosis as their life spans increase, individual variation occurs in this disease.

Efficacy and neurologic outcome of profound hypocapneic alkalosis for the treatment of persistent pulmonary hypertension in infancy

Twenty-three newborn infants with severe bilateral pulmonary disease and persistent pulmonary hypertension received mechanical ventilation to pH greater than 7.55 and PaCO2 less than 25 torr. Response, as defined by attainment of a PaO2 greater than 100 torr, occurred in 87% of patients. Analysis of sequential arterial pH determinations revealed a linear increase in the number of infants responding as arterial pH increased. However, individual patients varied greatly in the optimal pH necessary to correct hypoxemia (range pH 7.50 to 7.75). Sixteen patients who had received mechanical hyperventilation were observed for 11.1 +/- 2.3 months. Virtually all had normal growth and development on follow-up physical and neurologic examinations, often despite profound or prolonged alkalosis and hypocarbia. In 11 infants at a corrected gestational age of 1 year, Bayley Scales of Infant Development revealed normal mental developmental indices (mean 106.2 +/- 15.4) and normal, but significantly lower, psychomotor developmental indices (93.2 +/- 11.7) (P less than 0.005). Although response and short-term outcome of neonatal hyperventilation appear favorable, this technique should be reserved for critically ill infants, because its long-term effects on the central nervous system are unknown.

Effect of postnatal steroid administration on serum vitamin A concentrations in newborn infants with respiratory compromise

Antenatal administration of glucocorticoids accelerates the fetal maturation of the lung, liver, and gastrointestinal tract. ~-3 w e previously demonstrated a significant elevation of.serum retinol, retinol-binding protein, and transthyretin concentrations in the cord blood of newborn infants whose mothers received betamethasone antenatally. 4 It was unclear from that study, however, whether this represented an effect primarily on the mother, the placenta, or the fetus. Mammel et al. 5 and others 6 demonstrated that postnatal steroid administration decreases alveolar-arterial oxygen gradients and improves lung mechanics in bronchopulmonary dysplasia, The mechanism of action remains unknown. Vitamin A has also been implicated in the prevention and treatment of bronchopulmonary dysplasia by promoting normal lung development and healing. 78 On the basis of these studies, we investigated the effect of postnatal dexamethasone administration on the vitamin A status of 13 infants who were treated with steroids because of significant respiratory compromise.

Calcitonin gene-related peptide immunoreactivity in airway epithelial cells of the human fetus and infant

SummaryCalcitonin gene-related peptide-immunoreactive cells were identified within the epithelium of distal conducting airways in the human fetus and infant. Several peptides and amines, including calcitonin, have been identified previously within a specific population of airway epithelial cells. These cells, referred to as pulmonary neuroendocrine cells, are postulated to be airway chemoreceptors responsible for changes in ventilation and perfusion in response to changes in airway gas composition. Calcitonin gene-related peptide immunoreactive cells could be identified throughout the period of development studies (20 weeks gestation to 3 months of age), but were present in only limited numbers in less than 50% of individuals (n=23). In contrast, large numbers of calcitonin gene-related peptide immunoreactive cells were identified in 100% of infants (1–3 months, n=5) with bronchopulmonary dysplasia. The differential processing of mRNA transcribed from the calcitonin gene in neural and non-neural tissue suggests that calcitonin, rather than calcitonin gene-related peptide, is the primary product of translation in pulmonary neuroendocrine cells. However, considering the potent vasodilatory and bronchoconstrictive effects of calcitonin gene-related peptide, its presence in pulmonary neuroendocrine cells, even in small amounts, may be important in controlling pulmonary vaso- and/or bronchomotor tone. The presence of large numbers of calcitonin gene-related peptide immunoreactive cells in infants with bronchopulmonary dysplasia suggests that calcitonin gene-related peptide may be one further agent contributing to the pulmonary pathophysiology seen in this disease.

Treatment of pulmonary manifestations of gastroesophageal reflux in children two years of age or less

Apnea and worsening bronchopulmonary dysplasia as well as recurrent aspiration pneumonia have been found to be consequences of gastroesophageal reflux in infants and young children. Antireflux procedures are effective in preventing gastroesophageal reflux; however, the effect of this operation on the course of these respiratory problems in very young patients is not known. We reviewed the results in 51 patients 2 years of age or less who underwent an antireflux fundoplication for pulmonary problems attributable to severe gastroesophageal reflux unresponsive to medical treatment. Twenty-eight patients had recurrent episodes of aspiration pneumonia, 14 had nonimproving or worsening bronchopulmonary dysplasia, and 9 had unexplained apneic episodes. Seventy-three percent of these patients had coexisting congenital anomalies or acquired problems. No operative deaths and no major surgical complications occurred. There were eight late deaths occurring between 1 and 25 months postoperatively: three were due to associated congenital anomalies or acquired problems, three to sepsis, and two to sudden infant death syndrome. Of the 43 surviving children, 91 percent with preoperative recurrent aspiration pneumonia had no additional episodes after Nissen procedure. Eighty-eight percent of the infants with unexplained apneic episodes showed marked benefit and 83 percent of those with bronchopulmonary dysplasia had clinical improvement. There were no late problems attributed to the operation even when it was performed in preterm infants. Therefore, we recommend fundoplication for patients 2 years of age or less who have a persistent pulmonary problem attributed to gastroesophageal reflux that does not respond to medical therapy.

The effect of glucocorticosteroids on serum, liver, and lung vitamin A and retinyl ester concentrations.

Vitamin A and its active metabolites are important factors in promoting normal respiratory epithelial differentiation and growth. Glucocorticoids, often used to treat chronic lung diseases in infancy and childhood, are known to increase serum retinol concentrations. To determine the effects of exogenous steroids on serum retinol and retinal-binding protein concentrations (as well as on liver and lung total vitamin A, retinol, and retinyl ester concentrations), 32 weanling Sprague-Dawley rats were divided into four equal experimental groups. Eight animals were vitamin A sufficient and received 7 days of intraperitoneal dexamethasone at 0.5 mg/kg/day (group SD), 8 were vitamin A sufficient and received placebo (group SP), 8 were made vitamin A deficient and subsequently received dexamethasone (group DD), and 8 were vitamin A deficient and received placebo (group DP). Dexamethasone increased serum retinol concentrations in the SD group (2.27 ± 0.20 μmol/L) when compared with control (SP, 1.64 ± 0.46 n,mol/L, p < 0.001) as well as with pretreatment baseline values (1.21 ± 0.23 μmol/L, p < 0.001). Lung total vitamin A, retinol, and individual retinyl esters were depleted by 56 ± 19% in the SD group, whereas liver values were depleted by 36 ± 23%. In the vitamin A-sufficient groups the relative percentages of four major retinyl esters (palmitate, stearate, oleate, and linoleate) did not change in either tissue after steroid exposure. The vitamin A-deficient groups had no detectable tissue vitamin A, and dexamethasone did not increase serum retinol concentrations in the DD group. Serum retinol-binding protein concentrations were significantly higher in both steroid-treated groups when compared with control. Dexamethasone increases serum retinol and retinol-binding protein concentrations in vitamin A sufficient rats, apparently at the expense of both lung and liver total vitamin A, retinol, and retinyl ester concentrations. We speculate that the liver and lungs are two sources for the increase in serum retinol reported with glucocorticosteroids.

Prophylactic furosemide in severe respiratory distress syndrome: Blinded prospective study

To further characterize the place for furosemide in the treatment of newborn infants with respiratory distress syndrome requiring mechanical ventilation, we conducted a blinded, prospective study comparing early prophylactic use (1 mg/kg every 12 hours for four doses beginning at 24 hours of age) with prn use of this drug. Prophylactic administration of furosemide produced no beneficial effect on any measure of pulmonary function compared with use of this drug as needed (prn). However, patients receiving the prophylactic furosemide regimen were found to have more rapid postnatal weight loss, higher pulse rate, and greater sympathomimetic drug requirement during the period of diuretic administration. Patients in the prophylactic group did not demonstrate the moderate expansion in plasma volume between 48 and 96 hours of age seen in the control group. These data suggest that the prophylactic regimen produced an undesirable degree of volume depletion. Further studies should be conducted to develop objective criteria for the selection of the subgroup of patients with respiratory distress syndrome who may benefit from furosemide.