Jorge T. Rodriguez

Expression of Aromatase, Estrogen Receptor α and β, Androgen Receptor, and Cytochrome P-450scc in the Human Early Prepubertal Testis

The expression of aromatase, estrogen receptor α (ERα) and β (ERβ), androgen receptor (AR), and cytochrome P-450 side chain cleavage enzyme (cP450scc) was studied in prepubertal testis. Samples were divided in three age groups (GRs): GR1, newborns (1- to 21-d-old neonates, n = 5); GR2, postnatal activation stage (1- to 7-mo-old infants, n = 6); GR3, childhood (12- to 60-mo-old boys, n = 4). Absent or very poor detection of ERα by immunohistochemistry in all cells and by mRNA expression was observed. Leydig cells (LCs) of GR1 and GR2 showed strong immunostaining of aromatase and cP450scc but weak staining of ERβ and AR. Interstitial cells (ICs) and Sertoli cells (SCs) expressed ERβ, particularly in GR1 and GR2. Strong expression of AR was found in peritubular cells (PCs). For all markers, expression in GR3 was the weakest. In germ cells (GCs), i.e. gonocytes and spermatogonia, aromatase and ERβ were immunoexpressed strongly whereas no expression of ERα, AR, or cP450scc was detected. It is proposed that in newborn and infantile testis, testosterone acting on PCs might modulate infant LC differentiation, whereas the absence of AR in SCs prevents development of spermatogenesis. The role of estrogen is less clear, but it could modulate the preservation of an adequate pool of precursor LCs and GCs.

Intestinal surface area in infants with acquired monosaccharide intolerance.

Acquired monosaccharide intolerance is characterized by the malabsorption of all carbohydrates, resulting in profuse acidic diarrhea. Five infants with this syndrome, ranging from two to six months of age, were studied by measuring their ability to absorb glucose given by intestinal perfusion. Jejunal biopsies obtained at the time of perfusion were studied by light and electron microscopy, and surface area measurements were obtained. Glucose absorption and surface area were significantly decreased (P less than 0.005) during the acute phase of the disease and improved during convalescence. A linear correlation (r = 0.8757) was observed between the ability to absorb glucose and intestinal surface area. It is concluded that the loss of absorptive surface is a major cause of the reduced carbohydrate absorption and consequent diarrhea.

Treatment of skin irritation around enterostomies with cholestyramine ointment

Eight patients with inflammation of the skin about the cutaneous stoma responded to local application of a 20% cholestyramine ointment in a short period of time. Two children treated with the hydrophilic base (Aquaphor) alone did not respond to treatment. The ileal bile acid patterns of two children with ileostomies were found to be different from that of the control group. Ileostomy patients had a higher concentration for total bile acids and a higher percentage of free bile acids.

MORPHOLOGIC BASIS FOR GLUCOSE MALABSORPTION IN INFANTS WITH ACQUIRED MONOSACCHARIDE INTOLERANCE (AMI)

Infants with AMI have chronic acidic diarrhea secondary to malabsorption of all carbohydrates resulting in profound malnutrition. Four patients with AMF were studied by an intestinal perfusion technique. A triple lumen tube with a Pediatric Crosby capsule at the tip was introduced into the jejunum. A 10% glucose solution was infused through a proximal site 30 cm from the collecting point. 1% polyethylene glycol was added as a non-absorbable marker. Samples were obtained every 15 minutes and glucose absorption rate was calculated. After the perfusion, a jejunal biopsy was obtained for histology and disaccharidase assay.Glucose absorption increased from 9.2 to 17.3 mg/min after 1 month rehabilitation. Villous length increased with recovery. Lactase, sucrose and maltose enzymes remained low.A linear relationship exists between glucose absorption and villous length. This implies that impaired glucose absorption is related to decreased mucosal surface area. Work supported by: Ross Laboratory, David Underwood Trust, NASA Contract 90059, USPH RR-00188 and AM-05721-01.

462 TREATMENT OF ACUTE DIARRHEA WITH ORAL ELECTROLYTE SOLUTIONS

Fifty-two children 6 to 29 months with good nutritional status, and a mild to moderate dehydration secondary to acute diarrhea received ad libitum one of four oral electrolyte solutions for 48 hours. The solutions differed only in type and level of carbohydrate: 5% glucose, 5%, 10%, and 12.5% corn syrup solids (CS). Electrolyte levels were similar in all solutions (Na+ 30, K+ 20, C1−30 mEq/1). At 48 hours 47/52 (90%) were normally hydrated by clinical observations with no difference among treatments. Mean intakes (all subjects) were 138 ml/kg (day 1) and 153 ml/kg (day 2) with no difference among groups. In 48 hours urine specific gravity (1.012 to 1.008) and serum urea (15.0 to 9.6 mg/dl) decreased and serum sodium (134 to 137 mEq/1) increased with no difference among treatments. Stool weights were 36.1 g/kg (day 1) and 45.1 g/kg (day 2) with no difference among treatments. Greater numbers of glucose positive stools were observed with 10% and 12.5% CS solutions than with either 5% solution. Stool electrolytes were Na+20 and K+ 23 mEq/kg stool/day and did not differ as to treatment. Stools of 7/52 (14%) patients contained bacterial pathogens. Diarrhea worsened in patients in each group (12.5%CS, 7/13; 10%CS, 5/13, 5%CS 1/13; 5% glucose, 2/13). Oral electrolyte solutions with 30 mEq Na/liter were effective in rehydration and electrolyte maintenance. Solutions with 5% glucose or CS resulted in less carbohydrate malabsorption.

ROLE OF FREE BILE ACIDS IN ACQUIRED MONOSACCHARIDE INTOLERANCE (AMI)

Glucose malabsorption has been produced in experimental animals fed free bile acids. For this reason it is important to investigate the role of duodenal free bile acid concentrations in infants with AMI. Four subjects who manifested dehydrating diarrhea with acid stools and free fecal glucose in response to a 5 % glucose electrolyte mix were studied. They were compared to 5 infants with Acute non-pathogenic Diarrhea (AD). Duodenal samples were processed by gas-liquid chromatography for free and conjugated bile acids. Glucose absorption was studied by infusing a 10 % solution with 1 % PEG through a double lumen tube in the jejunum. Samples were recovered at 15 minutes intervals from a 30 cm. distal site. Total unconjugated bile acids (μg/ml) were 20.1 ± 8 in normal controls, 58.4 ± 27 in infants with AD and 319 ± 134 in AMI. A linear correlation exists between the concentration of free bile acids of the intestinal fluid and glucose transport ratef (r = 0.79 ). These observations support the role of altered bile acid metabolism in acquired glucose malabsorption.Work supported by: David Underwood Trust, NASA Contract 90059. NTH RR 00188, Mead Johnson Laboratories and AMA Goldberger Fellowship.

MODULAR FORMULA FOR WEANING INFANTS FROM TOTAL PARENTERAL NUTRITION (TPN)

Frequently, infants with chronic diarrhea and failure to thrive require TPN to overcome the intestinal absorptive defect. Weaning from TPN without exacerbation of diarrhea is difficult. We have developed a formula which can be structured to challenge the intestine sequentially with the various nutrient modules and concentrations. The Core formula is composed of whole casein and minerals calculated to deliver adequate electrolytes when used in a concentration cf 3 gms % protein. To this protein Core, fats and sugars can be added as needed and tolerated by the patient. When weaning from TPN, modules are added in 1 gm % increments every 12 hrs. starting with protein, fat and then carbohydrate. When the composition equals 3 gm % Core mix, 3.5 gm % fat and 6 gm % carbohydrate and this is tolerated for 1 week, the patient is switched to a proprietary formula which most closely matches. If a concentration is reached that causes diarrhea, it is maintained or slightly reduced until intestinal tolerance developes. In the past three years, more than 75 patients have been weaned to oral feedings in this manner with no difficulty. Work supported by: Ross Laboratory, David Underwood Trust, USPH RR-00188, and AM-05721-01.