Tokuzo Harada

Manganese Deposition in the Brain During Long-Term Total Parenteral Nutrition

BACKGROUND Manganese deposition was suspected in a pediatric patient who received long-term total parenteral nutrition. T1-weighted magnetic resonance images revealed high intensity areas in the globus pallidus. This study was designed to clarify if these abnormal findings were related to manganese deposition and clinical neurological manifestations. METHODS Whole-blood manganese concentrations were measured during manganese supplementation to total parenteral nutrition and after 5 months without manganese. Magnetic resonance images were also examined on each occasion and compared with the blood level of manganese. RESULTS The whole-blood manganese level during supplementation was 135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was 20 micrograms/L after a manganese-free period of 5 months. Accompanied with normalization of manganese level, abnormal high intensity lesions in the globus pallidus on T1-weighted images also disappeared. No neurological manifestation related to the high manganese level was recognized. CONCLUSIONS It is probable that the high manganese level was elicited by manganese supplementation to total parenteral nutrition. This high manganese condition was confirmed by the measurement of whole-blood manganese level, which was associated with the abnormal high intensity lesions on T1-weighted magnetic resonance images.

Gastric acid hypersecretion in short bowel syndrome in infants: association with extent of resection and enteral feeding.

Summary: To determine the frequency of gastric acid hypersecretion in infants with chronic malabsorption due to short bowel syndrome, acid secretory function was determined in 23 infants with malabsorption 2‐22 months following small bowel resection and in a control group of 14 chronically ill, age‐ and weight‐matched infants who did not undergo bowel resection. The prevalence of basal acid hypersecretion (defined as acid output 2 SD above the mean for the control group) was 17% (4 of 23). Basal gastric acid hypersecretion was associated with two factors: massive small bowel resection and initiation of enteral feeding. Basal acid hypersecretion was present on the initial study in 3 of 7 infants with less than one‐third of the small bowel remaining, but in only 1 of 16 with more than one‐third intact (p < 0.05). Hypergastrinemia was present in 3 of 6 infants following massive bowel resection, but in only 1 of 15 with more than one‐third intact (p < 0.05), but hypergastrinemia was not consistently associated with hypersecretion. In each of six previously unfed infants, a trial of enteral feeding resulted in increased basal and maximal acid output. Three infants developed basal acid hypersecretion during initiation of enteral feeding. There was no evidence of pentagastrin‐stimulated maximal acid hypersecretion in any of the infants.

Effects of alternate and simultaneous administrations of calcium and phosphorus on calcium metabolism in children receiving total parenteral nutrition.

The effects of alternate and simultaneous administrations of calcium (Ca) and phosphorus (P) on Ca metabolism in children receiving total parenteral nutrition (TPN) were examined. Eight children, aged 2 to 36 months, were studied. The following three solutions were administered: solution 1 contains Ca (533 mg/liter); solution 2 contains P (413 mg/liter); and solution 3 contains Ca (267 mg/liter) and P (207 mg/liter). Solutions 1 and 2 were administered alternately for 24-hr periods. (Results) I. During administration of solution 1, significant hypophosphatemia (4.39 +/- 0.26 mg/dl) and hypercalcemia (9.96 +/- 0.15 mg/dl) were observed and, conversely, during administration of solution 2, significant hypocalcemia (8.36 +/- 0.18 mg/dl) and hyperphosphatemia (6.16 +/- 0.27 mg/dl) were observed. During administration of solution 3, the serum levels of both minerals were maintained within the normal ranges (Ca 9.46 +/- 0.12 mg/dl, P 5.65 +/- 0.21 mg/dl). II. The urinary excretion of cyclic AMP was significantly lower during administration of solution 1 (6.67 +/- 0.45 nmol/mg creatinine (Cr] as compared with solution 3 (7.50 +/- 0.61 nmol/mg of Cr). On the other hand, the excretion was significantly higher during administration of solution 2 (11.55 +/- 1.58 nmol/mg of Cr) as compared with solution 3, indicating the existence of secondary hyperparathyroidism. III. The Ca and P retention rates were significantly higher with solution 3 (Ca 79.0 +/- 5.5%, P 73.2 +/- 7.2% of the intake) than with solutions 1 and 2 alternately (Ca 62.7 +/- 4.5%, P 49.2 +/- 9.3%). (Conclusions) Simultaneous administrations of Ca and P are preferable to their alternate administrations for Ca metabolism in children receiving TPN.

Meal-stimulated gastric acid secretion in infants.

Basal acid output and meal-stimulated acid output were measured in newborn infants after nasogastric infusion of 5% glucose and elemental formula, respectively. In six older infants (age range 6 to 31 months), basal acid output was 0.067 +/- 0.017 mmol/kg/hr and maximal acid output was 0.200 +/- 0.028 mmol/kg/hr. Meal-stimulated acid output in four of six older infants was 0.149 +/- 0.038 mmol/kg/hr. In eight healthy newborn infants basal acid output was 0.038 +/- 0.008 mmol/kg/hr; meal-stimulated acid output was 0.064 +/- 0.011 mmol/kg/hr (P less than 0.01). The time course of the secretory response to the elemental formula was as described previously after a protein meal in adults: the rate of acid secretion increased after 20 minutes and remained greater than the basal rate through the remainder of the 90 minute test period. These results demonstrate that in human newborn infants a mixed meal containing protein hydrolysate induces an acid secretory response that is qualitatively similar to but weaker than the response in older infants and adults.

Pulmonary hypertension associated with postoperative biliary atresia: Report of two cases

The authors report on 2 patients with biliary atresia in whom pulmonary hypertension (PH) developed in the long-term follow-up after hepatoportoenterostomy. Both had portal hypertension and had undergone distal splenorenal shunt. Dyspnea developed around 14 to 15 years of age. Cardiac catheterization showed pulmonary artery pressure (PAP) of 99/37 (58) and 67/32 (48) mm Hg, respectively, which did not respond to vasodilators. One patient suffered from respiratory tract infection followed by right heart failure and subsequent death at 20 years of age. Postmortum histological findings exhibited severe thickening of the pulmonary artery wall. PH may grow insidiously even after successful hepatoportoenterostomy. Careful monitoring of PAP and hemodynamic response of PAP to vasodilators is essential for evaluating the reversibility of PH and making treatment decisions.

Hypophosphatemic Rickets Accompanying Congenital Microvillous Atrophy

This report concerns an 11‐year‐old boy who manifested hypophosphatemic rickets associated with congenital microvillous atrophy (CMA). He had been suffering from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition (TPN) since he was 67 days old. At 4 years of age, intestinal biopsy resulted in a diagnosis of CMA. He was admitted to our hospital complaining of leg pain at the age of 11. Laboratory data revealed hypophosphatemia, elevated serum 1,25‐dihydroxyvitamin D (1,25(OH)2D) levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. This case is different from X‐linked hypophosphatemic rickets but similar to hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in terms of hypercalciuria and elevated serum 1,25(OH)2D levels. The effectiveness of phosphate treatments used here is also similar to that used for HHRH. However, this type of hypophosphatemic rickets is unique in that phosphate leaking into the intestine plays an important role in its pathogenesis.

Long-term Follow-up of Gastroplasty in a Patient with Prader-Willi Syndrome

To prevent the development of metabolic disturbances caused by overeating, we performed vertical banded gastroplasty in an adult woman with Prader-Willi syndrome. Her fasting blood sugar (FBS) and urinary sugar excretion (US) decreased during 6 months after the surgery under strict dietary control in the hospital. The insulin response to oral glucose at 6 months after surgery was as good as in the normal controls. A barium meal study in the 11th postoperative month revealed that the staple line was partially ruptured. After this, FBS and US increased, and the glucose tolerance and insulin response worsened. At 24 months, US was still less than preoperative US, and the oral glucose tolerance test showed a better result than before operation. At 29 months, her condition was brought under control with use of Glibenclamide. At 60 months, her FBS and US were at the same level as before operation. She was doing a part-time job. In conclusion, the effect of gastroplasty in preventing worsening of glucose metabolism in a case of Prader-Willi syndrome lasted satisfactorily for 24 months in spite of the partial breakdown of the staple line.

Transient neonatal hypothyroidism probably related to immaturity of thyroidal iodine organification

roid hormone replacement then may cause thyrotroph regression and expose the pituitary gland and sella to CSF pressure or arachnoid pulsations, which may produce an empty sella. 13 In general, only a minority of patients with empty sella develop pituitary hormone deficiencies, 14 so additional damage to the pituitary gland must occur in some individuals. One might wonder whether slower thyroxine treatment (e.g., less than full replacement dosage) might have altered the development of an empty sella and hypopituitarism. This has been suggested by McVie, ~3 although we know of no studies to support this recommendation. Our patient was initially given a relatively 10w dose of thyroxine, 1.67 /~g/kg body weight, and subsequently required increased dosage. Evidence is accumulating that pituitary enlargement and subtle visual field defects and pituitary alterations occur more commonly with primary hypothyroidism than previously appreciated. Our case report outlines the full spectrum of these changes during childhood, when the development of hGH deficiency has more impact. The initial CT scan was obtained somewhat serendipitously; with the diagnosis of primary hypothyroidism, we would recommend CT scan of the brain only if the patient has signs of increased intracranial pressure or visual field deficits. With pituitary enlargement or mild visual field defects, we believe a conservative approach with thyroxine therapy and close observation is warranted. If the expected clinical response is not seen (in particular, failure to return to normal or catch-up growth rate), the clinician must consider the development of hypopituitarism, which may be associated with an empty sella. We thank Douglas Livermore, M.D., for referring the

Metabolic changes following gastroplasty in Prader-Willi syndrome--a case report.

A vertical banded gastroplasty was performed in an adult female patient with Prader-Willi syndrome in an attempt to prevent the metabolic deterioration caused by polyphagia. After her operation, the patient felt satiated with the scheduled amount of food and one month later, her fasting blood sugar concentration (FBS) decreased from 521 to 125 mg/dl, and her urinary sugar excretion (US) from 257 to 9g/day. Both glucose tolerance and insulin secretion were also improved. However, these parameters subsequently became worse after dietary control was lost since the surgical procedure alone was unable to continue to suppress the insatiable desire to eat food. Both her glucose tolerance and insulin secretion by the 31st postoperative month were better than before the surgery, but worse than at one month after the surgery. At the end of the 34th postoperative month, even under the temporary administration of 0.625 mg/day of glibenclamide, her FBS was 158 mg/dl and US, 38.1 g/day. Her body weight had also increased to over her preoperative value. Based on these results, we conclude that the effect of gastroplasty to prevent metabolic deterioration in our patient with Prader-Willi syndrome gradually diminishes.

Urinary sulfated bile acid concentrations in infants with biliary atresia and breast-feeding jaundice.

A selective screening for an early identification of biliary atresia (BA) and hepatobiliary disease is advocated 1 using tests for urinary bilirubin and serum direct bilirubin in the third week of life. However, venepuncture is not desirable in small infants for a primary screening purpose at a clinic. The urinary excretion of sulfated bile acid (USBA) increases with cholestasis through an activated alternate metabolic pathway of bile acid. 2 A direct enzymatic assay of USBA has been reported as a sensitive and rapid method of detecting cholestatic jaundice, replacing measurements of serum-direct bilirubin for selective screening for BA and neonatal hepatitis syndrome. 3 We have measured USBA in BA before surgery and other infantile cholestatic conditions since 1996. The present report summarizes the feasibility of this urinary test as a screening modality.