Pulmonary bombesin in experimentally induced asbestosis in rats

The pulmonary levels of immunoreactive bombesin in normal rat lungs and rat lungs exposed to asbestos were determined. Experimental asbestosis was induced in rats by a single intratracheal injection of 5 mg or 10 mg UICC standard Canadian Chrysotile B while sham-operated control rats received only the saline carrier. At 1, 3, 6, and 9 months following instillation, 5 animals of each group were sacrificed and the lungs removed. A section was kept for morphologic analysis, while the remaining portion was submitted to acid extraction and later measured for bombesin content by radioimmunoassay (RIA). The Chrysotile B-exposed tissues displayed the characteristic features typical of the fibrotic state associated with asbestosis one month following exposure and thereafter. The pulmonary bombesinlike immunoreactivity ranged from 4.5-7.5 pmoles/g tissue in normal rat lung, and these levels remained unchanged at 1 and 3 months after asbestos exposure. However at 6 and 9 months, significant increases ranging between 2 and 2.5 fold were observed. The initial increases in bombesin levels occurred at a later time (6 months) than those already observed for vasoactive intestinal peptide (VIP) (3 months). However, VIP levels plateaued at 9 months, while those of bombesin were still increasing. High-pressure liquid chromatography (HPLC) coupled with RIA demonstrates the presence of two bombesin-immunoreactive peaks in normal rat lung, the major one coeluting with the mammalian bombesinlike peptide gastrin-releasing peptide (GRP) and the other one being presumably a C-terminal portion of GRP. These data indicate that immunoreactive bombesin and VIP are selectively increased at different times following asbestos instillation and that these changes occur after the onset of fibrosis and the appearance of well-defined fibrotic lesions.     

Localization of bombesin-like peptides in frog gastric mucosa.

Antibodies against synthetic bombesin C-terminal nonapeptide were used to investigate the presence of bombesin-like immunoreactivity by radioimmunoassay and to identify bombesin (like)-containing cells by indirect immunofluorescence in the gastrointestinal tract of the frog species Rana pipiens, Rana catesbeiana, and Xenopus laevis. Bombesin-like immunoreactivity was localized by radioimmunoassay in the stomach of the three frog species. Immunofluorescent endocrine-appearing cells were seen only in the mucosal glands of the gastric antrum and fundus of the same species.     

Neonatal thromboembolism

In neonates and infants numerous clinical and environmental conditions such as the use of central lines, cardiac diseases and polycythemia, renal diseases such as congenital nephrotic syndrome and neonatal hemolytic uremic syndrome, peripartal asphyxia, infants of diabetic mothers, dehydration, septicemia, necrotizing enterocolitis, acute respiratory distress syndrome, and extracorporeal membrane oxygenation lead to elevated thrombin generation and subsequent thrombus formation. Genetic prothrombotic defects [protein C, protein S and antithrombin deficiency, mutations of coagulation factor V and factor II, elevated lipoprotein (a)] have been established as risk factors for thromboembolic events. The interpretation of laboratory results relies on age-dependent normal reference values. Because appropriate clinical trials are missing in these age groups, treatment recommendations are adapted from small-scale studies in neonates and infants and from guidelines relating to adult patient protocols. Secondary long-term anticoagulation should be administered on an individual basis.     

Neurotensin, substance P, gastrin/cholecystokinin, and bombesin in the intestine of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus): immunochemical detection and effects on electrophysiological characteristics.

The distribution of neurotensin-, substance P-, gastrin/cholecystokinin/carerulein- and bombesin-like immunoreactivities has been studied in the gut of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus) using immunohistochemistry and radioimmunoassay; the electrophysiological effects of these peptides on the intestinal epithelium were also examined with the Ussing-type chamber technique. Neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactivities were present in endocrine cells in both species. Substance P- and bombesin-like immunoreactive endocrine cells were present in the intestine of the tilapia. Neurotensin-like immunoreactivity was observed in varicose fibers and nerve cell bodies in the muscle layers and myenteric plexus of both species, whereas nerve fibers showing substance P-like immunoreactivity were found in the goldfish only. Using radioimmunoassays, neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactive materials were detected in intestinal extracts of both species. The amounts of substance P- and bombesin-like material were below detection level. The ion selectivity of the intestinal epithelium of both species was modulated by exogenously applied neurotensin. This effect was blocked by tetrodotoxin in the tilapia but not in the goldfish. In the tilapia, neurotensin may act via stimulation of a cAMP-dependent increase of the Cl- conductance of the tight junctions, whereas in the goldfish, neurotensin induced, via an unknown messenger, a transient decrease of the cation selectivity without a decrease in the resistance. Substance P, cholecystokinin, and bombesin were without effect on the electrophysiological characteristics of the epithelium.     

Pulmonary vascular endothelial growth factor-C in development and lung injury in preterm infants

RATIONALE: In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear. OBJECTIVES: We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants. METHODS: Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA. RESULTS: Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid. CONCLUSIONS: The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.     

Melatonin concentration in the umbilical artery and vein in human preterm and term neonates and neonates with acute fetal distress

In order to assess the existence of a rhythmic secretion of melatonin (aMT) in newborns and whether this rhythm is affected by neonatal stress, we studied 112 newborns classified in three groups: normal babies delivered at term, preterm infants born before the 38th week, and babies with fetal distress. Melatonin was measured by RIA in the umbilical artery and vein at the time of birth. Melatonin levels in umbilical arterial and venous blood showed a diurnal rhythm in all groups. Melatonin levels in umbilical cord artery and vein were closely related. Nocturnal melatonin levels were increased in newborns with acute fetal distress in comparison with normal term and preterm neonates. These results suggest that (1) a rhythm of aMT secretion exists in newborns, although it cannot be determined whether this rhythm is of maternal or fetal origin and (2) neonatal stress (acute fetal distress) increases aMT production during the night in comparison with normal term and preterm neonates.     

Cystic fibrosis: an unusual neonatal presentation

In mechanically ventilated neonates it is not uncommon to observe obstructive atelectasis from various causes. However it is extremely rare to see mucous plugging and massive pulmonary atelectasis in the absence of infection, aspiration, and respiratory distress syndrome in the first couple of days of life. In this report we describe a neonate born with cystic fibrosis (CF) who presented to us with hypoxic respiratory failure, pulmonary hypertension, and hypercarbia without lactic acedemia from sticky mucous plugging and massive lung collapse. Neonatal respiratory distress and wide spread pulmonary atelectasis has not been reported in infants born with CF.     

Urine bombesin-like peptide elevation precedes clinical evidence of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth weight infants, associated with oxygen therapy, barotrauma, and/or infections. Improved medical care has led to a paradoxically increased incidence of BPD due to greater infant survival. Early prediction of BPD has proven challenging. Increased pulmonary neuroendocrine cells containing bombesin-like peptide immunoreactivity occur in infants with BPD. We hypothesized that elevated urine bombesin-like peptide levels precede BPD. One hundred thirty-two infants, 28-weeks gestation or less, were studied. Urine bombesin-like peptide levels, determined by radioimmunoassay, were normalized for creatinine. BPD was defined as oxygen dependence at 36 weeks postmenstrual age. A first urine bombesin-like peptide level greater than 20,000 pg/mg creatinine (12,500 fmol/mg) between postnatal days 1-4 occurred among 54% of the infants who later developed BPD (p < or = 0.001), versus 10% among non-BPD infants (specificity 90%). Multivariable logistic regression analyses revealed that elevated urine bombesin-like peptide levels are associated with BPD (odds ratio 9.9, 95% confidence interval: 3.4, 29) (p < or = 0.001) after adjusting for all confounding factors. Thus, elevated bombesin-like peptide levels in these infants at 1-4 days after birth are associated with a 10-fold increased risk of developing BPD. Utilizing urine bombesin-like peptide for screening might permit early therapeutic interventions to reduce disease progression and could provide a target for new preventive therapies.     

Acute respiratory failure in hyperleukocytotic acute myeloid leukemia: The role of perfusion lung scintigraphy

A patient with acute hyperleukocytotic myelogenous leukemia who presented with acute respiratory distress is reported. Clinical manifestations included dyspnea, tachypnea, hyperventilation, and cyanosis. Blood gas analysis revealed hypoxemia, hypocapnia, and metabolic acidosis. Chest X-ray and perfusion lung scanning were normal. Pulmonary leukostastis syndrome (PLS) was later confirmed at autopsy. In a patient with hyperleukocytosis from acute nonlymphocytic leukemia and respiratory distress, a normal perfusion lung scintigraph should make one consider the PLS.     

固尔苏预防新生儿呼吸窘迫综合征的疗效分析

目的探讨固尔苏（肺泡表面活性物质制剂）预防新生儿呼吸窘迫综合征的疗效。方法将45例同条件早产儿分为两组,观察组21例于生后2h内经气管注入固尔苏;对照组24例未使用固尔苏,比较两组早产儿呼吸窘迫综合征发生率、需要呼吸机治疗的比例、常见并发症的发生率及预后。结果观察组早产儿呼吸窘迫综合征发生率、需要呼吸机治疗的比例及常见并发症的发生率均较对照组减低（P〈0．05）。结论高危早产儿生后应尽早预防性使用固尔苏,可有效降低呼吸窘迫综合征的发病率,减少并发症的发生和呼吸机的应用,提高早产儿生存质量。     

Neuropeptides in pig sphincter of Oddi,bile duct,gallbladder, and duodenum

To better understand the complex structure and function of the sphincter of Oddi (SO), the occurrence and localization of nine neuropeptides, including vasoactive intestinal polypeptide (VIP), bombesin, neuropeptide Y, peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), galanin, substance P, serotonin, and somatostatin, were studied by immunohistochemical methods in the pig SO. The SO innervation was compared to gallbladder, common bile duct, and duodenal innervation. Specimens from the SO, gallbladder, common bile duct, and duodenum demonstrated a rich network of nerves, as suggested by light microscopy and confirmed by a myeline marker S-100. SO demonstrated very strong immunoreactivity for VIP, strong immunoreactivity for neuropeptide Y and galanin, moderate immunoreactivity for PHI and CGRP, and borderline immunoreactivity for bombesin and substance P. Serotonin and somatostatin immunoreactivity was also observed, not in the nerves, but in some of the epithelial cells. The gallbladder innervation was virtually identical to the SO innervation, whereas common bile duct and duodenal innervation were slightly different. To our knowledge this is the first time that galanin- and PHI-like immunoreactivities have been observed in the SO. Our observations suggest that these peptides, along with VIP, neuropeptide Y, and CGRP, might play a role in the neural control of biliary motility.     

Radioimmunoassay of vasoactive intestinal peptide immunoreactivity in guinea pig respiratory tract

Although vasoactive intestinal peptide (VIP) has been suggested to be the neurotransmitter of non-adrenergic and non-cholinergic (NANC) inhibitory nerves, its physiological functions and movements in the airway are obscure. In this study, VIP immunoreactivity in the respiratory tract from guinea pigs was measured as a preliminary experiment to elucidate its functions. VIP immunoreactivity was measured by radioimmunoassay. The rate of VIP disappearance during extraction was 52.5 +/- 17.4 (mean +/- SD)%. The dose-response curve of tissue extract almost paralleled the standard curve of authentic VIP. VIP immunoreactivity of tracheas was 939.9 +/- 262.1 pg/g wet weight and that of extrapulmonary bronchi was 858.0 +/- 241.1 pg/g wet weight. Although VIP immunoreactivity of lung extracts was not detectable in 14 samples out of 23, the value of 9 samples was 111.7 +/- 61.5 pg/g wet weight. These results suggest that there may be more VIP immunoreactivity present in tracheas and extrapulmonary bronchi than in lungs.     

Effect of volume and dose on the pulmonary distribution of exogenous surfactant administered to normal rabbits or to rabbits with oleic acid lung injury

Administration of exogenous lung surfactant to infants with or at risk for respiratory distress syndrome has been demonstrated to improve gas exchange and survival; administration of surfactant to patients with the adult respiratory distress syndrome is currently undergoing clinical evaluation. Although it is currently assumed the optimal effect will occur when administered surfactant is distributed homogeneously throughout the lung, little is known of the influence of variables inherent in the administration procedure on subsequent distribution. To address this question, we studied the effect of the volume size in which the surfactant is suspended for instillation, and demonstrated a marked relationship in the normal rabbit lung between this volume and the subsequent homogeneity of surfactant distribution. In the rabbit lung that was acutely injured by oleic acid, this relationship was not evident. Concentration of administered surfactant was not demonstrated to be of major influence on its distribution after administration. Our results focus attention on the importance of parameters of the administration procedure, and also demonstrate the usefulness of the techniques used for determination of surfactant distribution.     

A bombesin immunoreactive peptide in milk.

Immunoreactivity to the amphibian peptide bombesin was found in instant nonfat dry milk (ca. 0.7 ng/ml) and in the whey of whole or skim bovine milk (ca. 1.2 ng/ml) even after ultracentrifugation. The soluble immunoreactivity was associated with a peptide exhibiting the following characteristics: (i) parallel displacement in an immunoassay using an antiserum recognizing bombesin amino acid residues 5-8; (ii) separation from both gastrin-releasing peptide and amphibian bombesin by gel filtration--the approximate Mr was 3,200; (iii) denaturation in urea, reduction by dithiothreitol, and acetylation by iodoacetamide had no effect on its elution profile by gel-filtration chromatography and the aggregation of added bombesin to milk proteins or peptides was not observed; (iv) reversed-phase HPLC separated milk immunoreactivity from gastrin-releasing peptide and bombesin; (v) digestion by trypsin yielded a smaller immunoreactive peptide fragment, whereas nearly all immunoreactivity was lost by treatment with alpha-chymotrypsin; and (vi) the level of immunoreactivity was unaffected by boiling. These data show that milk is an exogenous source of bombesin-like immunoreactivity, which may account for the increase of gastric acid and gastrointestinal hormone levels after the consumption of milk.     

Functional residual capacity and passive compliance measurements after antenatal steroid therapy in preterm infants

Studies in preterm animal models have shown that antenatal corticosteroids enhance lung maturation by improving a variety of physiologic variables, including lung volumes. Changes in lung volume of preterm infants treated with a full course of antenatal steroids have not been investigated. We hypothesized that a full course of antenatal steroids would significantly increase functional residual capacity (FRC) in treated vs. untreated preterm infants. The objective of our study was to compare FRC and respiratory mechanics in steroid treated vs. untreated preterm infants. FRC and passive respiratory mechanics were prospectively studied within 36 hr of life in 20 infants (25-34 weeks of gestation) who had received a full course of antenatal steroids and in 20 matched untreated preterm infants. FRC was measured with the nitrogen washout method, and respiratory mechanics with the single-breath occlusion technique. Preterm infants who received steroids (n = 20; mean birth weight = 1,230 g; gestational age = 28.8 weeks) had a significantly higher FRC (29.5 vs. 19.3 mL/kg; P < 0.001) than untreated infants (n = 20; birth weight = 1,202 g; gestational age = 28.5 weeks). Passive respiratory system compliance was also increased in treated vs. untreated infants (P < 0.05). In conclusion, FRC and passive respiratory system compliance were significantly improved in preterm infants (25-34 weeks gestation) treated with a full course of antenatal steroids, compared to matched untreated infants. Although this study was not randomized, it confirms that antenatal steroids have important effects on pulmonary function that may contribute to a decreased risk of respiratory distress syndrome in treated preterm infants.     

Inhaled ribavirin therapy in adult respiratory syncytial virus-induced acute respiratory distress syndrome

Respiratory syncytial virus (RSV) infection-induced acute respiratory distress syndrome (ARDS) in previously healthy adults is rare, but the overall mortality rate is 40-60%. Inhaled ribavirin is approved for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to RSV. We present the case of an adult female with RSV pneumonia-induced ARDS who was successfully treated with inhaled ribavirin and whose pulmonary function was restored to near normal. The role of inhaled ribavirin in adults is controversial, but it might have a therapeutic potential for severe RSV infection-induced ARDS in adults.     

Differential thresholds of neuromedins B-, C-, and bombesin-induced anorexia and crop-emptying rate in chicks

Neuromedin B (NMB) and neuromedin C (NMC) are homologs of bombesin and are distributed throughout both the brain and gastrointestinal tract. The physiological roles of these bombesin-like peptides in chicks (Gallus gallus) have not been documented. Therefore, the purpose of the present study was to measure the effects of these bombesin-like peptides on food intake, crop-emptying rate and body temperature in chicks, and then to compare these effects with those of bombesin. Intracerebroventricular (ICV, 5 nmol) and intraperitoneal (IP, 300 nmol/kg) injections of NMB, NMC, and bombesin significantly decreased food deprivation-induced food intake. When ICV injected (5 nmol), all three peptides significantly reduced crop-emptying rate. IP injection of NMC and bombesin (300 nmol/kg) also reduced crop-emptying rate while NMB did not. The magnitude of food intake suppression and crop-emptying rate reduction were greater for bombesin than NMB and NMC. ICV and IP injections of NMB, NMC and bombesin did not affect cloacal temperature. In sum, the present study suggests that central and peripheral NMB and NMC are associated with reduced food intake and crop-emptying of chicks, but these effects are weaker than those of bombesin.     

PITUITARY ACTH DEPENDENT CUSHING''S SYNDROME DUE TO ECTOPIC PRODUCTION OF A BOMBESIN-LIKE PEPTIDE BY A MEDULLARY CARCINOMA OF THE THYROID

A 41-year-old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin-like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin-like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin-like peptide, causing excessive pituitary ACTH secretion.     

Incidence and short-term outcome of acute lung injury in mechanically ventilated children.

The aim of this study was to determine the incidence and short-term outcome of mechanically ventilated children suffering from acute lung injury (ALI) on a paediatric intensive care unit (PICU). Between January 1 1998 and January 1 2000, all mechanically ventilated children were evaluated using the criteria of an American-European Consensus Conference. Of the 443 children eligible for analysis, 44 (9.9%) were diagnosed as suffering from ALI. Of these, 79.5% developed the acute respiratory distress syndrome (ARDS); 54.5% (24 of 44) fulfilled the ARDS criteria at inclusion and 25% (11 of 44) later. PICU mortality for ALI was 27.3% (12 of 44) and within the ARDS subgroup 31.4% (11 of 35). Of the 12 children who died, 11 had ARDS; the main cause of death was cerebral damage (seven of 12). Acute lung injury and acute respiratory distress syndrome are rare diseases on a paediatric intensive care unit with a high mortality. Most of the children with acute lung injury develop acute respiratory distress syndrome. In the acute respiratory distress syndrome subgroup, mortality is higher than in the acute lung injury nonacute respiratory distress syndrome subgroup. Further investigations should confirm prognostic factors (e.g. respiratory parameters) for prediction of outcome.     

Acute respiratory distress syndrome by cytomegalovirus infection in an immunocompetent infant

A 2-month-old female infant was admitted with progressive respiratory distress, fever, and diagnosed with acute respiratory distress syndrome (ARDS). The primary pulmonary pathogen was proven to be cytomegalovirus (CMV) from bronchoalveolar lavage fluid, urine, and blood specimens. Other immunologic findings were normal. CMV-induced ARDS has not been reported previously in immunocompetent infants.