Nonfatal congenital alveolar dysplasia due to abnormalities of NO synthase isoforms.

Congenital alveolar dysplasia (CAD) is a rare disorder thought to represent alveolar growth arrest at the canalicular stage of development. An infant with CAD diagnosed on lung biopsy is reported, her respiratory problems resolved spontaneously and she was doing well at follow-up. The infant additionally suffered from systemic hypertension and hypertrophic pyloric stenosis. In conclusion, we speculate that the association of CAD with systemic hypertension and hypertrophic pyloric stenosis might be explained by abnormalities of isoforms of nitric oxide synthase (NOS) resulting in congenital deformities involving smooth muscles.

Distribution of heme oxygenase-2 in nerves and interstitial cells of Cajal in the normal pylorus and in infantile hypertrophic pyloric stenosis.

CONTEXT: Interstitial cells of Cajal (ICCs) are pacemaker cells, which are of fundamental importance in regulating gastrointestinal motility. Recent evidence suggests that carbon monoxide is a neurotransmitter involved in neurotransmission between ICC and smooth muscle cells. Heme oxygenase-2 (HO-2) is the major physiological mechanism for the generation of carbon monoxide in the enteric nervous system. OBJECTIVE: To investigate the immunocolocalization of HO-2 and ICCs in the normal pylorus and in infantile hypertrophic pyloric stenosis (IHPS). DESIGN: Specimens from 18 infants with IHPS and 8 control specimens were examined using double-immunostaining with c-Kit and HO-2 antibodies. The immunolocalization was detected with the help of confocal laser scanning microscopy. RESULTS: Abundant HO-2 immunoreactivity was found in ICCs in the smooth muscle layer of normal pylorus. There was a decrease in the number of ICCs and lack of HO-2 immunoreactivity in ICCs in IHPS. CONCLUSIONS: The results of the present study provide the first evidence for the presence of HO-2 in ICCs in the normal human pylorus. The lack of ICCs and HO-2 in IHPS suggests impaired intracellular communication between ICCs and smooth muscle cells, contributing to motility dysfunction in IHPS.

Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis.

PURPOSE: The aim of this study was to study nitric oxide synthase (NOS) immunohistochemistry in the pyloric muscle and establish the role of nitric oxide in pyloric stenosis. METHODS: Pyloric muscle biopsy specimens were obtained from 20 patients with pyloric stenosis during pyloromyotomy. Ten control specimens without pyloric disease were obtained from autopsy performed less than 4 hours after death on age-matched babies who died of other causes. Tissues were fixed in 4% paraformaldehyde immediately. A monoclonal antibody against the neuronal form of NOS (bNOS) was used for immunohistochemistry. RESULTS: Immunohistochemistry showed activity of bNOS in the control specimens and some pyloric stenosis specimens. This shows that NOS is present in the pylorus in normal cases as well as in a few cases of pyloric stenosis. CONCLUSIONS: NOS deficiency leading to lack of locally available nitric oxide causes a failure of smooth muscle relaxation. This may account for the cause of pyloric stenosis in infants. However, this study shows that this is true probably only in a subset of cases. The etiology of pyloric stenosis may still be multifactorial. Further investigations are required regarding the etiology of pyloric stenosis. J Pediatr Surg 36:616-619.

[The function of the digestive processes in the stomach and small intestine in complicated peptic ulcer]. / Sostoianie pishchevaritel'nykh protsessov v zheludke i tonkoi kishke pri oslozhnennoi iazvennoi bolezni.

On the basis of investigations designed to study the condition of intragastric proteolysis and membrane digestion in the small intestine in 148 patients it has been found out that peptic ulcer is accompanied by enhancement of digestive processes in the stomach and by decrease thereof in the small intestine. With the development of peptic ulcer complications digestive disorders get aggravated, which fact leads to various manifestations of the enteral syndrome. A conclusion has been reached that study into intragastric proteolysis and membrane digestion can be useful in the objective evaluation of the activity and degree of severity of the ulcerous process as well as in the functional assessment of results of the treatments administered.

Altered messenger RNA expression of the neuronal nitric oxide synthase gene in infantile hypertrophic pyloric stenosis.

Nitric oxide (NO) has been described as a mediator of smooth muscle relaxation in the mammalian gastrointestinal tract. The enzyme neuronal nitric oxide synthase (NOS) catalyzes the formation of NO. We examined the expression of the neuronal NOS gene at the messenger RNA (mRNA) level in pyloric smooth-muscle biopsy specimens from six patients with infantile hypertrophic pyloric stenosis (IHPS) using a reverse transcription-polymerase chain reaction (RT-PCR) technique. For controls, smooth-muscle layer specimens of pylorus (n=3), ileum (n=2), and colon (n=2) were used. With 31 cycles of PCR reaction, control specimens revealed detectable signals for neuronal NOS mRNA. In contrast, signals of IHPS specimens were undetectable in five cases and very weak in one. By increasing the PCR to 37 cycles, detectable signals for neuronal NOS mRNA were observed in all IHPS specimens, but they were significantly weaker than those of controls. Since a low level of neuronal NOS mRNA may lead to impaired production of NO, our observations indicate that the excessively contracted, hypertrophied pyloric muscle in IHPS is a result of reduced expression of the neuronal NOS gene at the mRNA level.

Targeted disruption of the neuronal nitric oxide synthase gene.

By homologous recombination, we have generated mice that lack the neuronal nitric oxide synthase (NOS) gene. Neuronal NOS expression and NADPH-diaphorase (NDP) staining are absent in the mutant mice. Very low level residual catalytic activity suggests that other enzymes in the brain may generate nitric oxide. The neurons normally expressing NOS appear intact, and the mutant NOS mice are viable, fertile, and without evident histopathological abnormalities in the central nervous system. The most evident effect of disrupting the neuronal NOS gene is the development of grossly enlarged stomachs, with hypertrophy of the pyloric sphincter and the circular muscle layer. This phenotype resembles the human disorder infantile pyloric stenosis, in which gastric outlet obstruction is associated with the lack of NDP neurons in the pylorus.

Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis.

BACKGROUND: Hypertrophic pyloric stenosis is a common infantile disorder characterized by enlarged pyloric musculature and gastric-outlet obstruction. Its physiopathologic mechanism is not known, but a defect in pyloric relaxation (pylorospasm) has been postulated. Nitric oxide is a mediator of relaxation in the mammalian digestive tract, raising the possibility that pylorospasm could be caused by a defect in nitric oxide production. Since neuronal nitric oxide synthase and NADPH diaphorase are identical, we used the NADPH diaphorase histochemical reaction to study the distribution of nitric oxide synthase in pyloric tissue from patients with infantile hypertrophic pyloric stenosis. METHODS: We studied pyloric tissue from nine infants with infantile hypertrophic pyloric stenosis and seven control infants and children. Cryostat sections were processed for NADPH diaphorase histochemical analysis. A polyclonal tau antiserum was used to identify the enteric nervous system by immunohistochemical methods. RESULTS: NADPH diaphorase activity was restricted to the enteric nervous system and blood vessels. In the pyloric tissues from the control patients, intense diaphorase activity was present in the nerve fibers of the circular musculature, in the neurons and nerve bundles of the myenteric plexus, and in some nerve fibers of the longitudinal musculature. In the pyloric tissues from patients with infantile hypertrophic pyloric stenosis, the enteric nerve fibers in the hypertrophied circular musculature were enlarged and distorted and did not contain diaphorase activity, whereas the activity in the myenteric plexus and the longitudinal musculature was preserved. CONCLUSIONS: We suggest that a lack of nitric oxide synthase in pyloric tissue is responsible for pylorospasm in infantile hypertrophic pyloric stenosis.

[The digestive processes of the stomach and small intestine in complicated peptic ulcer]. / Pishchevaritel'nye protsessy v zheludke i tonkoi kishke pri oslozhnennoi iazvennoi bolezni.

Investigation of the state of intraventricular proteolysis and membraneous digestion in the small intestine in 148 patients revealed that ulcer disease is accompanied by potentiation of the digestive processes in the stomach and their reduction in the small intestine. With appearance of complications of ulcer disease, the disorders of digestion deteriorated. This resulted in different manifestations of the enteral syndrome. It is concluded that examination of the intraventricular proteolysis and membraneous digestion may be used for objective evaluation of the activity and grade of severity of the ulcer process as well as for functional evaluation of treatment results.

Determination of cholinesterase and acetylcholinesterase in amniotic fluid. Uses in prenatal diagnosis and quality control.

The determination of acetylcholinesterase (AChE) has been shown to be as specific as alphafetoprotein (AFP) for the prenatal detection of open neural tube defects although AFP remains the method of choice. This paper describes a semi-automated technique for the analysis of acetylcholinesterase in amniotic fluid that: A) reduces the cost of the procedure; B) allows for a larger number of samples to be run at a time; and C) provides for more accurate and reproducible procedures and results. Six fetuses with neural tube defects (2 with gastroschisis and 3 where one twin was dead) were detected and found to have elevated AChE, TChE and 2 bands by electrophoresis. Quality control procedures using both pure enzyme and amniotic fluid with low and high levels of the enzyme are described. The analysis of 340 amniotic fluids of normal pregnancies indicates that the normal value for AChE is 5.17 +/- 2.63 mU/ml (97% confidence interval for the mean 4.84-5.49 mU/ml. A group of 27 abnormal pregnancies provides evidence that fetal vomiting and regurgitation, fetal demise, multiple cysts syndrome, idiopathic IUGR, arthrogryposis multiplex, hydrocephaly (stenosis of aqueductus), trisomy 21, trisomy 18, hydronephrosis, pyloric stenosis, heart malformation, ectopia cordis and multiple gestation produce elevated levels of pseudocholinesterase (PChE) in amniotic fluid. The use of pseudocholinesterase levels in amniotic fluid for prenatal diagnosis is proposed and discussed in view of its elevated levels in abnormal pregnancies where AChE is normal. The normal values for PChE are 23.86 mU/ml (mean) and 5.83 for standard deviation. Electrophoretic analysis was performed on all samples with values higher than one standard deviation above the mean.(ABSTRACT TRUNCATED AT 250 WORDS)

beta-Glucuronidase in gastric aspirate after oral cimetidine in the diagnosis of carcinoma of the stomach.

The activity of beta-glucuronidase was studied in the gastric aspirate from normal individuals, cases of duodenal ulcer with pyloric stenosis and carcinoma of the stomach. The optimum pH for the activity of this enzyme in the gastric aspirate is 4.0 to 5.5. Cimetidine, a H2-receptor antagonist, was administered orally to obtain the optimum pH for the enzyme activity, when the pH of the gastric aspirate was less than 4.0. It is observed that the enzyme activity in cases of carcinoma of the stomach is markedly elevated (p less than 0.01), when compared with other cases in this study. It is suggested that the elevated enzyme activity in the gastric aspirate could be used as a biochemical marker in the diagnosis of carcinoma of the stomach.

Esterolytic activity of blood serum in infants with hypertrophic pyloric stenosis.

Esterolytic activity of blood serum was determined in infants with hypertrophic pyloric stenosis and in healthy control children. The substrates hydrolyzed mainly by arylesterase (EC. 3.1.1.2), i.e. p-nitrophenyl esters of acetic, propionic and butyric acid were used. It was found that in infants with hypertrophic pyloric stenosis the rate of p-nitrophenyl propionate hydrolysis was significantly higher than that of the acetate or butyrate. In control group children all three substrates were hydrolysed at similar rates, and these were significantly lower than in infants with hypertrophic pyloric stenosis.

On the source of lipase activity in gastric contents.

--A convenient assay procedure for determination of the activity of pharyngeal lipase (gastric content lipase), using a long chain triglyceride as substrate, is described. Lipase activity in extracts of rat tongue, salivas collected from the upper esophageal pouch from two human newborns with congenital esophageal atresia and in gastric content obtained from an infant with pyloric stenosis were studied. Optimal lipase activities of the three enzyme sources were found in the same pH-range. During hydrolysis the composition of the products formed were also similar. The data presented indicate that at least some of the lipase activity which is responsible for lipolysis in the stomach of the newborn, originates in pregastric tissues.

Role of feeding on lipase activity in gastric contents.

Lipase activity was recorded in gastric contents collected from healthy term and preterm neonates. In contrast to pancreatic lipase activity this lipase activity was higher at pH 5.5 than at pH 8.0 and it was more resistent to acid inactivation. Lipase activity was found in gastric contents from all infants who were regularly fed, but was not present in gastric contents from some infants when collected before regular feeding was established. During test meals lipase activity in gastric contents increased considerably in all infants studied. During such a test meal there was a progressive relative decrease in triglycerides whilst diglycerides showed a relative increase suggesting an active lipolytic process in the stomach. An assay procedure for determination of lipase activity in gastric contents is also described.

[Jaundice associated with congenital hypertrophic pyloric stenosis (author's transl)]. / Ictericia asociada a estenosis hipertróifica de píloro

The clinical and biological findings in six infants with congenital hypertrophic pyloric stenosis with associated jaundice are described. Pathogenesis of this association is not known but current hypothesis are based on either a decrease in the activity of hepatic glucuronyl transferase or an increase in the activity of intestinal glucuronidase. Correction of dehydration and alkalosis does not modify the hyperbilirubinemia which only disappears after pyloromiotomy.