Four cases of bleeding diathesis in children due to congenital plasminogen activator inhibitor-1 deficiency.

Congenital plasminogen activator inhibitor-1 (PAI-1) deficiency is an extremely rare disorder characterized by a bleeding diathesis that begins in childhood due to hyperfibrinolysis as a result of decreased PAI-1 activity. We now present 4 unrelated pediatric cases of congenital PAI-1 deficiency. All 4 patients had a history of recurrent episodes of subcutaneous bleeding beginning in early childhood. These episodes were characterized by abnormal prolonged bleeding after trauma, tooth extraction, and surgical procedures, as well as by rebleeding following initial hemostasis. The 2 female patients both had symptoms compatible with hypermenorrhea. The family history was positive in 2 of the 4 patients. Hemostatic screening studies in all 4 patients revealed no abnormalities. Testing for factor XIII antigen, von Willebrand factor antigen, ristocetin cofactor activity, alpha(2)-plasmin inhibitor (alpha2PI) activity, and plasminogen activity was normal. The euglobulin lysis times were shortened in all cases as compared with those in normal control subjects. None of the patients had elevated tissue plasminogen activator (tPA) antigen levels, but PAI activity was markedly decreased in all cases. Three of the patients also had reduced levels of PAI-1 antigen. There tended to be a reduction in tPA-PAI-1 complex in all cases. In addition, 2 patients had elevated PIC (plasmin-alpha2PI complex). Tourniquet tests were performed in 2 patients, with no appreciable rise in PAI-1 activity or PAI-1 antigen levels. The administration of tranexamic acid clearly improved hemorrhagic symptoms in these patients. We considered PAI-1 deficiency to be the likely etiology of the congenital bleeding diatheses in these 4 cases.

Single-channel thin-fiber and Nd:YAG laser temporomandibular joint arthroscope: development and preliminary clinical findings.

This study evaluated the development and preliminary results of a single-channel thin-fiber and Nd:YAG laser temporomandibular joint arthroscope. No articular damage from the arthroscopic procedure and laser lysis was observed in any of the joints when the arthrotomy was performed. All three disk perforations found by the arthroscope were confirmed at the time of the arthrotomy, and in these joints the tip of the arthroscope could be advanced into the inferior joint. The nine joints, where only arthroscopic laser lysis was performed, were followed up and the results were satisfactory.

Infantile granulomatous urachal abscess with acute localized peritonitis and appendicitis.

Infected urachal remnants in early childhood are occasionally seen. However, intraperitoneal penetration of an infected urachal remnant, resulting in acute peritonitis, is rare. We report a case of infantile granulomatous urachal abscess extending into the peritoneum and appendix. The diagnosis and treatment of urachal abscess in childhood are discussed.

[A girl presenting clinical course and neuroimagings on MRI compatible with Pelizaeus-Merzbacher disease].

A 5-year-old girl who showed congenital nystagmus and mental and motor developmental delay, is described. Auditory brainstem responses (ABR) revealed wave I at normal latency, but all of the following waves were absent. In T2-weighted images, magnetic resonance imaging (MRI) demonstrated diffuse high intensity area of cerebral white matter, suggesting extensive dysmyelination or demyelination. She has not shown any deterioration through her clinical course. Subsequent MRI examinations did not demonstrate a progressive disorder. These findings suggest the possibility of Pelizaeus-Merzbacher (P-M) disease in this patient, which is a rare form of sudanophilic leukodystrophy, transmitted by an X-linked recessive mutant gene. It is reported that the proteolipid protein, one of the major proteins of myelin, was absent in classical type P-M disease, resulting in dysmyelination. Because chromosomal study showed the normal female karyotype and no family history of a similar disease was found in this case, it might be different from classical P-M disease. Since P-M disease may be heterogeneous, more detailed chromosomal analysis in each case of congenital hypomyelination will give a clue to clarify the pathogenesis of P-M disease and other disorders showing failure in myelination.

[Anesthetic management for partial tongue resection in a patient with Beckwith-Wiedemann syndrome].

A 14-month-old baby weighing 4300 g was a giant infant with macroglossia. Exomphalos was not present, but diastasis recti abdominis was observed. The patient was therefore diagnosed as having Beckwith-Wiedemann syndrome (EMG syndrome). Other characteristic signs such as neonatal hypoglycemia, hemihypertrophy, and a small ventricular septal defect were also recognized, but nephromegaly or hepatomegaly was not present. Tongue reduction by wedge resection was performed under general anesthesia. Some of the problems associated with anesthetic management in this syndrome are hypoglycemia, airway obstruction and cardiovascular status. After induction with increasing concentration of halothane (0.5-4.0%) and 66% nitrous oxide in oxygen, a nasotracheal tube was inserted. Endotracheal intubation was easy without using a neuromuscular blocking agent. Anesthetic maintenance was accomplished with nitrous oxide 66% in oxygen and halothane 0.5-1.0% and no neuromuscular blocking agent was used. The plasma glucose level was kept within normal ranges during and after the operation by infusion of acetate Ringer's solution with 5% glucose. The postoperative progress was uneventful.

Serum levels of vitamin D metabolites in children receiving total parenteral nutrition.

Serum levels of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) were measured on 19 occasions in seven children receiving total parenteral nutrition (TPN). The daily intakes of vitamin D3 ranged from 44 to 540 IU/day, and all serum samples were obtained after the same daily intake of vitamin D3 for more than 1 month. There was a significant positive correlation between serum 25-OHD levels and parenteral vitamin D3 intakes (r = 0.90, p less than 0.01). In this study, serum 25-OHD levels in all cases taking 200 to 360 IU/day of vitamin D3 were within the normal range. On the other hand, no significant correlation was found between serum 1,25-(OH)2D levels and vitamin D3 intakes, and serum 1,25-(OH)2D levels were normal or elevated in all cases.

Total parenteral nutrition with a new amino acid solution for infants.

The currently available, commercially prepared amino acid mixtures for intravenous usage do not result in completely normal plasma amino acid patterns. Taking into consideration the known imbalances that occur with the commercial preparations, we designed a new amino acid solution (AF). This solution was prepared to contain a low concentration of those amino acids usually found in increased concentrations in plasma during the course of total parenteral nutrition (TPN) with a commercially prepared product (CF) and a high concentration of branched-chain amino acids and arginine. Plasma amino acid concentrations were determined for nine infants receiving CF (Group A) and eight infants receiving AF (Group B) as the protein source while on TPN for 5 days. These data were compared to 2-h postprandial values obtained from breast-fed, growing infants serving as controls. In comparison with controls, the plasma concentrations of threonine, glycine, methionine, phenylalanine, tryptophan, and lysine were higher in infants in group A, while those of taurine, alanine, valine, cystine, isoleucine, and proline were lower. In group B, the levels of valine and leucine were slightly higher, while those of alanine, cystine, tyrosine, histidine, and proline were lower. Mean nitrogen balances in groups A and B were + 112 and + 170 mg/kg/day, respectively. Therefore, our new amino acid solution may be better for infants receiving TPN.

Breath hydrogen test in infants and children with blind loop syndrome.

Breath hydrogen production after oral lactose loading was examined in infants and children with stagnant loop syndrome, blind loop syndrome, or both. All six infants under 3 years of age had bacteriological evidence of small intestinal colonization. The characteristics of the breath hydrogen test in this syndrome are: (a) extremely high basal excretion of breath hydrogen (after overnight fasting); (b) an earlier and greater breath hydrogen value (0.293 +/- 0.201 ml/min/m2: mean +/- SD) after oral lactose administration than formed in lactose malabsorption alone (0.050 +/- 0.041 ml/min/m2); and (c) the observation of a sustained hydrogen rise over several hours. This investigation demonstrated that the breath hydrogen test is a promising and noninvasive tool for diagnosing blind (or stagnant) loop syndrome.

Study of ammonia metabolism in a patient with ornithine transcarbamylase deficiency using an 15N tracer.

Ammonia metabolism was studied in an 8-year-old girl with ornithine transcarbamylase (OTC) deficiency, using 15N-tracer. Changes in the incorporation of 15N into amino acids and urea were examined after 15NH4Cl administration. The recovery of total 15N in the urine of the patient in 3 days was 28.5% of the administered 15N whereas that of a control was 69.3%. They were mostly urea. The recovery of 15N-urea in the patient was 28.8% of the control in 1 day, 32% in 2 days and 33.3% in 3 days after the administration of 15NH4Cl. A larger amount of 15N was incorporated into glutamine (alpha-amino N) and glutamate and 15N was incorporated more rapidly into alanine, asparagine and serine in the patient than in the control. The incorporation into ornithine was less in the patient than in the control.

Organic acid metabolism in a patient with ornithine transcarbamylase deficiency.

Serum and urinary organic acids in a 9-year-old girl with ornithine transcarbamylase deficiency were investigated. The urinary excretion of alpha-ketoglutarate (alpha-KG) and citrate were abnormally high. An inverse linear correlation was found between the plasma ammonium and alpha-KG levels when the plasma ammonium level was less than 200 micrograms/dl, but not at higher levels, suggesting that on overloading with ammonium, its route of metabolism and compensating mechanism are not functionally normal. After administration of NH4Cl, plasma and urinary levels of alpha-KG, pyruvate and citrate increased, but the urinary succinate level decreased slightly. After oral administration of citrate the plasma alpha-KG level increased and the ammonium level decreased transiently. Our results suggest that administration of citrate or alpha-KG is not effective for reducing hyperammonemia in ornithine transcarbamylase deficiency.

Failure of p-aminobenzoic acid screening test to diagnose pancreatic insufficiency in Shwachman's syndrome.

The 6-h urine recovery of p-aminobenzoic acid (PABA) following the administration of a standard dose of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BTPABA) was performed in 13 control subjects and two siblings with Shwachman's syndrome. The control subjects showed a recovery of 67 +/- 12.1% (mean +/- 1 SD) of the administered dose, consistent with previously reported values. Unexpectedly, the recovery of PABA in two siblings with Shwachman's syndrome was found to be 67 and 63%, respectively. The values are well within the normal range. In these siblings, fecal chymotrypsin activities were very low when measured with N-acetyl-L-tyrosyl-ethyl ester (ATEE) as substrate, but were normal when BTPABA was the substrate. The duodenal juice of the younger affected child following pancreozymin-secretin stimulation showed very low chymotrypsin activity against ATEE, BTPABA, and N-benzoyl-L-tyrosyl-ethyl ester. These findings suggest that there may be BTPABA-splitting activity in the lower bowel of these siblings with Shwachman's syndrome. This activity might be that of enteric bacteria or of the intestinal mucosa.