Point of Care Ultrasound to Identify Diaphragmatic Dysfunction after Thoracic Surgery.

BACKGROUND: Postoperative diaphragmatic dysfunction after thoracic surgery is underestimated due to the lack of reproducible bedside diagnostic methods. We used point of care ultrasound to assess diaphragmatic function bedside in patients undergoing video-assisted thoracoscopic or thoracotomic lung resection. Our main hypothesis was that the thoracoscopic approach may be associated with lower incidence of postoperative diaphragm dysfunction as compared to thoracotomy. Furthermore, we assessed the association between postoperative diaphragmatic dysfunction and postoperative pulmonary complications. METHODS: This was a prospective observational cohort study. Two cohorts of patients were evaluated: those undergoing video-assisted thoracoscopic surgery versus those undergoing thoracotomy. Diaphragmatic dysfunction was defined as a diaphragmatic excursion less than 10 mm. The ultrasound evaluations were carried out before (preoperative) and after (i.e., 2 h and 24 h postoperatively) surgery. The occurrence of postoperative pulmonary complications was assessed up to 7 days after surgery. RESULTS: Among the 75 patients enrolled, the incidence of postoperative diaphragmatic dysfunction at 24 h was higher in the thoracotomy group as compared to video-assisted thoracoscopic surgery group (29 of 35, 83% vs. 22 of 40, 55%, respectively; odds ratio = 3.95 [95% CI, 1.5 to 10.3]; P = 0.005). Patients with diaphragmatic dysfunction on the first day after surgery had higher percentage of postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.001). Radiologically assessed atelectasis was 46% (16 of 35) in the thoracotomy group versus 13% (5 of 40) in the video-assisted thoracoscopic surgery group (P = 0.040). Univariate logistic regression analysis indicated postoperative diaphragmatic dysfunction as a risk factor for postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.002). CONCLUSIONS: Point of care ultrasound can be used to evaluate postoperative diaphragmatic function. On the first postoperative day, diaphragmatic dysfunction was less common after video-assisted than after the thoracotomic surgery and is associated with postoperative pulmonary complications.

Typical patterns of expiratory flow and carbon dioxide in mechanically ventilated patients with spontaneous breathing.

Incomplete expiration of tidal volume can lead to dynamic hyperinflation and auto-PEEP. Methods are available for assessing these, but are not appropriate for patients with respiratory muscle activity, as occurs in pressure support. Information may exist in expiratory flow and carbon dioxide measurements, which, when taken together, may help characterize dynamic hyperinflation. This paper postulates such patterns and investigates whether these can be seen systematically in data. Two variables are proposed summarizing the number of incomplete expirations quantified as a lack of return to zero flow in expiration (IncExp), and the end tidal CO2 variability (varETCO2), over 20 breaths. Using these variables, three patterns of ventilation are postulated: (a) few incomplete expirations (IncExp < 2) and small varETCO2; (b) a variable number of incomplete expirations (2 ≤ IncExp ≤ 18) and large varETCO2; and (c) a large number of incomplete expirations (IncExp > 18) and small varETCO2. IncExp and varETCO2 were calculated from data describing respiratory flow and CO2 signals in 11 patients mechanically ventilated at 5 levels of pressure support. Data analysis showed that the three patterns presented systematically in the data, with periods of IncExp < 2 or IncExp > 18 having significantly lower variability in end-tidal CO2 than periods with 2 ≤ IncExp ≤ 18 (p < 0.05). It was also shown that sudden change in IncExp from either IncExp < 2 or IncExp > 18 to 2 ≤ IncExp ≤ 18 results in significant, rapid, change in the variability of end-tidal CO2 p < 0.05. This study illustrates that systematic patterns of expiratory flow and end-tidal CO2 are present in patients in supported mechanical ventilation, and that changes between these patterns can be identified. Further studies are required to see if these patterns characterize dynamic hyperinflation. If so, then their combination may provide a useful addition to understanding the patient at the bedside.

Effect of positive end-expiratory pressure on pulmonary shunt and dynamic compliance during abdominal surgery.

BACKGROUND: General anaesthesia decreases pulmonary compliance and increases pulmonary shunt due to the development of atelectasis. The presence of capnoperitoneum during laparoscopic surgery may further decrease functional residual capacity, promoting an increased amount of atelectasis compared with laparotomy. The aim of this study was to evaluate the effects of different levels of positive end-expiratory pressure (PEEP) in both types of surgery and to investigate whether higher levels of PEEP should be used during laparoscopic surgery. METHODS: This prospective observational study included 52 patients undergoing either laparotomy or laparoscopic surgery. Three levels of PEEP were applied in random order: (1) zero (ZEEP), (2) 5 cmH2O and (3) 10 cmH2O. Pulmonary shunt and ventilation/perfusion mismatch were assessed by the automatic lung parameter estimator system. RESULTS: Pulmonary shunt was similar in both groups. However, in laparotomy, a PEEP of 5 cmH2O significantly decreased shunt when compared with ZEEP (12 vs 6%; P=0.001), with additional PEEP having no further effect. In laparoscopic surgery, a significant reduction in shunt (13 vs 6%; P=0.001) was obtained only at a PEEP of 10 cmH2O. Although laparoscopic surgery was associated with a lower pulmonary compliance, increasing levels of PEEP were able to ameliorate it in both groups. CONCLUSION: Both surgeries have similar negative effects on pulmonary shunt, while the presence of capnoperitoneum reduced only the pulmonary compliance. It appears that a more aggressive PEEP level is required to reduce shunt and to maximize compliance in case of laparoscopic surgery.

Development of clinical tools to estimate the breathing effort during high-flow oxygen therapy: A multicenter cohort study.

INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

From intensive care to rehabilitation: survey on the satisfaction with care received during prolonged hospitalization for COVID-19 at a northern Italian university hospital.

OBJECTIVE: Investigating the experiences perceived by COVID-19 inpatients is a fundamental research area that is starting to be explored. For this reason, our objective was to provide the first Italian survey on COVID-19 inpatients' satisfaction, obtained through a self-completed questionnaire previously used in a reference study in a UK cohort of COVID-19 patients. SUBJECTS AND METHODS: Hospitalized COVID-19 patients (>20 days) admitted to Ferrara University Hospital who underwent rehabilitation during their hospital stay were invited to complete an anonymous questionnaire. The survey's questions explored the patients' satisfaction with the health services received, and their completion took place approximately one year after hospitalization. Information on sex, number of wards, ICU stays, and hospital discharge dates was collected. RESULTS: Sixty-two completed questionnaires were analyzed. The average overall satisfaction score obtained from the answers indicated by the participants in the tenth question was 4.7 out of 5.0. Very positive responses were observed for information about discharge plans, privacy, management of pain, sleep quality, and feeling of safety. The possibility of being consulted about medications and side effects received a very low satisfaction score. Considering overall satisfaction, no significant differences were noted for sex or ICU stay. The obtained results were almost superimposable to those reported in the cohort of COVID-19 patients of the reference study. CONCLUSIONS: This survey suggested that COVID-19 patients' healthcare satisfaction was high. Nevertheless, some areas must be improved, such as the communication and involvement of the patients in the decision-making of care and the discussion about medications or possible side effects.

Insulin production and resistance in cystic fibrosis: effect of age, disease activity, and genotype.

AIM: To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD). SUBJECTS AND METHODS: One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic ß-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR). RESULTS: The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes. CONCLUSIONS: IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, ß-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.

LMA Supreme™ vs i-gel™--a comparison of insertion success in novices.

Two new supraglottic airway devices, the LMA Supreme™ (LMA) and the i-gel™, offer potential benefits when inserted by inexperienced operators. This study compared the insertion success rate and ventilation profile between the LMA Supreme and the i-gel when inserted by operators without previous airway management expertise. Following a short lecture and manikin training, airway novices were randomly allocated to insert either the LMA Supreme or the i-gel into 80 patients undergoing breast surgery. The primary outcome was first-time success rate, and secondary outcomes were overall success rate, insertion time, airway leak pressure, tidal volume during pressure controlled ventilation at 17 cmH(2)O, and adverse events. First-time insertion success rate was significantly higher for the LMA Supreme than the i-gel (30/39 (77%) vs 22/41 (54%); p = 0.029). Significantly more placement failures occurred with the i-gel (6 vs 0, p = 0.025). Mean (SD) leak pressure (29 (8) vs 23 (11) cmH(2)O, p = 0.007) and expired tidal volume (PCV 17 cmH(2)O) (785 (198) vs 654 (91), p = 0.001) were significantly greater with the LMA Supreme than with the i-gel, respectively. More patients complained of pharyngolaryngeal pain with the LMA Supreme than with the i-gel (17/39 (44%) vs 8/41 (20%); p = 0.053). We found better first time success rate, fewer failures, and a better seal with the LMA Supreme compared with the i-gel, indicating that the LMA Supreme may be preferable for emergency airway use by novices.

Recurrent pneumothorax after cesarean delivery in the critically ill pregnant with severe COVID-19 ARDS: a case report.

OBJECTIVE: Few data are available on the ICU management and on the possible respiratory complications of invasively ventilated pregnant patients affected by COVID-19 pneumonia, especially in the early phase of pregnancy. Tension pneumothorax has been previously described as a rare cause of respiratory failure after delivery, but its occurrence in the postpartum of COVID-19 patient has not been reported yet. We hereby describe the ICU management of a 23rd gestational week pregnant woman who underwent invasive mechanical ventilation, prone positioning, and cesarean delivery during her ICU stay for COVID-19 related pneumonia. Moreover, we focused on the occurrence and management of recurrent tension pneumothorax after the cesarean delivery. CASE REPORT: A 23rd gestational week pregnant woman was admitted to the ICU for a COVID-19 bilateral pneumonia and underwent invasive mechanical ventilation and prone positioning. Cesarean delivery was planned during the ICU stay, while the patient was receiving invasive mechanical ventilation. After delivery, the patient experienced a recurrent pneumothorax that required the positioning of multiple chest drains. CONCLUSIONS: In pregnant critically ill COVID-19 patients, mechanical ventilation management is particularly challenging, especially in the postpartum period. Prone positioning is feasible and can improve oxygenation and respiratory system compliance, while tension pneumothorax must be suspected if the respiratory function suddenly deteriorates after delivery.

Osteoblasts extracellular matrix induces vessel like structures through glycosylated collagen I.

Extracellular matrix (ECM) plays a fundamental role in angiogenesis affecting endothelial cells proliferation, migration and differentiation. Vessels-like network formation in vitro is a reliable test to study the inductive effects of ECM on angiogenesis. Here we utilized matrix deposed by osteoblasts as substrate where the molecular and structural complexity of the endogenous ECM is preserved, to test if it induces vessel-like network formation by endothelial cells in vitro. ECM is more similar to the physiological substrate in vivo than other substrates previously utilized for these studies in vitro. Osteogenic ECM, prepared in vitro from mature osteoblasts at the phase of maximal deposition and glycosylation of collagen I, induces EAhy926, HUVEC, and HDMEC endothelial cells to form vessels-like structures and promotes the activation of metalloproteinase-2 (MMP-2); the functionality of the p-38/MAPK signaling pathway is required. Osteogenic ECM also induces a transient increase of CXCL12 and a decrease of the receptor CXCR4. The induction of vessel-like networks is dependent from proper glycosylation of collagens and does not occur on osteogenic ECMs if deglycosylated by -galactosidase or on less glycosylated ECMs derived from preosteoblasts and normal fibroblasts, while is sustained on ECM from osteogenesis imperfecta fibroblasts only when their mutation is associated with over-glycosylation of collagen type I. These data support that post-translational glycosylation has a role in the induction in endothelial cells in vitro of molecules conductive to self-organization in vessels-like structures.

Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future.

Hypoxic-ischemic encephalopathy, also referred as HIE, is a type of brain injury or damage that is caused by a lack of oxygen to the brain during neonatal period. The incidence is approximately 1.5 cases per 1000 live births in developed countries. In low and middle-income countries, the incidence is much higher (10‒20 per 1000 live births). The treatment for neonatal HIE is hypothermia that is only partially effective (not more than 50% of the neonates treated achieve an improved outcome). HIE pathophysiology involves oxidative stress, mitochondrial energy production failure, glutaminergic excitotoxicity, and apoptosis. So, in the last years, many studies have focused on peptides that act somewhere in the pathway activated by severe anoxic injury leading to HIE. This review describes the pathophysiology of perinatal HIE and the mechanisms that could be the target of innovative HIE treatments.

Procollagen I COOH-terminal fragment induces VEGF-A and CXCR4 expression in breast carcinoma cells.

The COOH-terminal fragment of procollagen type I (C3) is produced in tissues with high synthesis of collagen I, such as in breast cancer stroma and in bone. We previously demonstrated that C3 is chemoattractant for breast carcinoma and endothelial cells, and that in tumor cells it induces expression and activation of metalloproteinases (MMP) -2 and -9. Here we demonstrate that C3 induces expression of vascular-endothelial growth factor (VEGF) and of CXCR4, the receptor of the CXCL12/SDF-1 chemokine, in MDA MB 231 breast cancer cells. We show that the changes in gene expression and motility induced by C3 occur in a timely succession and are mediated by multiple and different signaling pathways. C3 induces early phosphorylation of p38/MAPK. Induction of VEGF expression requires continual activity of p38/MAPK and of Protein Kinase C (PKC). Pro-MMP-2 and -9 are induced through a signaling pathway involving G0alpha.i protein, and cell migration requires the activity of a combination of these signaling pathways. Our results suggest that C3 acts as a stromal-derived, cancer-promoting agent active in inducing the migratory phenotype and the survival of cancer cells and determining timely changes in their gene expression that establish conditions promoting tumor angiogenesis and invasion.

[Immigrant pregnancy and neonatal morbidity]. / Gestante inmigrante y morbilidad neonatal.

INTRODUCTION: Over the past few years immigration has become an important growth issue in Spain, with the subsequent social, economic and health impact it produces. OBJECTIVE: To analyze the characteristics of immigrant pregnancy and its neonatal morbidity. METHOD: Prospective, descriptive, and cross-sectional study, which includes live-born infants born in the Hospital de Sabadell, from the 1st of September until the 31st of December, 2004. All demographic data were collected, together with details of the pregnancy, the labour, the infant and its associated morbidity. RESULTS: There were 902 births during this period, of which 159 (17.6%) were immigrant pregnancies, with Latin Americans and Moroccans predominant. About 83.3% of immigrant pregnancies where of mothers who have lived in Spain for less than 5 years. The average age of immigrant pregnancies was 27 years (p<0.001), multiparous is more frequent (p<0.001) and have a lower control of pregnancy than non-immigrant (p=0.001). The average gestational age is similar between both groups, nevertheless, the average weight is significantly higher in immigrant women newborns (p<0.05). About 36.5% of the newborns are admitted with their mother o in the neonatal unit, with the main reason for admission being the risk of infection with a predominance between the newborns of immigrant pregnancies (p=0.05). The number of newborns admitted in the neonatal unit is similar in both groups. CONCLUSIONS: This study allowed us to look at characteristics of immigrant pregnancies and draw conclusions in providing the necessary medical assistance for this new and growing population.

Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation.

The integrity of the insulin-like growth factor (IGF) system is essential for normal fetal growth. Cytokine and IGF-IGFBP relationships have been shown in specific tissues, but it is unknown whether these occur in the placenta. We aimed to assess possible differences in the IGF system depending on gestational age (GA) from week 35 to 40, and to study relationships of IL-6 with components of the IGF system in the placenta and newborn infant. We followed 32 normal births and collected whole villous tissue and cord serum. Total RNA was extracted from the placenta samples, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins were assayed in placenta lysates and cord serum using specific commercial kits. Two groups of subjects (Group 1, 35-37 weeks GA, N=12 and Group 2, 38-40 weeks GA, N=20) were studied. In placenta, IGF-I mRNA was more abundant than IGF-II mRNA at all times and together with IGFBP-1mRNA were less expressed at term. IGFBP-2 and IL-6 mRNAs were higher after week 37 GA. IL-6 and IGFBP-2 gene expression were closely related. The corresponding proteins showed similar differences to the genes but IGF-I was undetectable in the lysates, whereas IGF-II was abundant. IGFBP-2 concentrations were very high and greater than those of IGFBP-1. In the newborn, no difference was seen in any cord serum protein after week 35 GA. IGFBP-1 was negatively correlated with parameters of neonatal size. In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA.

Transfusion of stored red blood cells in critically ill trauma patients: a retrospective study.

OBJECTIVE: The many published studies on the effects of the transfusion of stored red blood cells on clinical outcomes yielded discordant results. Therefore, we chose to study patients with severe trauma. The clinical outcomes considered included in-hospital mortality, the occurrence of sepsis, length of stay in intensive care unit and in hospital, and days of mechanical ventilation. PATIENTS AND METHODS: We selected all patients with traumatic injury, who received at least 2 red cell units in the first day of admission. Patients were divided into two groups: those who had received fresh red cells only (fresh group) and those who had received at least one "old" red cell unit (old group). The red cells were considered fresh if they had been stored <14 days. RESULTS: The fresh and old groups included 376 and 321 patients, respectively. Baseline demographic and clinical characteristics were comparable between the groups. However, old group received more red cell and plasma units during whole hospital stay (red cells: 11 ± 7 vs 6 ± 4, p < 0.001; plasma: 7 [0-9] vs 3 [0-6]). Among outcomes, only length of stay in intensive care unit (old vs fresh: 18 ± 9 vs 12 ± 8 days, p < 0.001) and in hospital (77 ± 35 vs 45 ± 30 days, p < 0.001) differed significantly between groups. The association remained statistically significant in a multivariate analysis including known confounding factors. CONCLUSIONS: Patients with major trauma transfused with old (≥14 days) red cells had a longer length of stay in intensive care unit and in hospital, without any difference in mortality, occurence of sepsis or days of mechanical ventilation.

A methodological approach for determination of maximal inspiratory pressure in patients undergoing invasive mechanical ventilation.

BACKGROUND: Maximal inspiratory pressure (MIP) can help to evaluate inspiratory muscle strength. However its determination in ventilated patients is cumbersome and needs special equipment. We hypothesized that MIP could be obtained by using the expiratory hold knob of the ventilator. The aim of this study was to verify whether: 1) the end expiratory occlusion technique can be used for MIP determination; and 2) if this technique provides different results compared to those obtained by the traditional method of MIP calculation. METHODS: We studied 23 consecutive patients undergoing mechanical ventilation for acute respiratory failure. The MIP was determined by two different methods, both based on occluding the airway for 20 seconds. This occlusion was obtained either by pressing the expiratory hold knob of the ventilator; or by detaching the patient from the ventilator circuit and using a noiseless pneumatic shutter placed on the inspiratory line of a two-way valve that allows expiration but prevents inspiration. RESULTS: The average values of MIP obtained by using either the hold knob of the ventilator or the noiseless pneumatic shutter were -46±14 cmH2O and -56±13 cmH2O, respectively. The linear regression analysis showed a significant correlation between MIPVent and MIPOcc (r2=0.95), although the Bland- Altman analysis revealed that they are not clinically comparable. CONCLUSION: MIP can be easily determined at the bedside by pressing the expiratory hold knob of ventilator. However, MIPVent and MIPOcc are different in terms of absolute value probably because they were determined at diverse lung volume.

Esophageal pressure measurements under different conditions of intrathoracic pressure. An in vitro study of second generation balloon catheters.

BACKGROUND: The aim of this study was to evaluate in vitro the accuracy of second generation esophageal catheters at different surrounding pressures and filling volumes and to suggest appropriate catheter management in clinical practice. METHODS: Six different esophageal catheters were placed in an experimental chamber at four chamber pressures (0, 10, 20 and 30 cmH2O) and at filling volumes ranging from 0 to 10 mL. The working volume was defined as the volume range between the maximum (Vmax) and minimum (Vmin) volumes achieving acceptable accuracy (defined by a balloon transmural pressure ± 1 cmH2O). Accuracy was evaluated for a standard volume of 0.5 mL and for volumes recommended by manufacturers. Data are shown as median and interquartile range. RESULTS: In the four conditions of chamber pressure Vmin, Vmax and working volume were 1.0 (0.5, 1.5), 5.3 (3.8, 7.1), and 3.5 (2.9, 6.1) mL. Increasing chamber pressure increased Vmin (rho=0.9; P<0.0001), that reached 2.0 mL (1.6-2.0) at 30 cmH2O. Vmax and working volumes differed among catheters, whereas Vmin did not. By injecting 0.5 mL and the minimum recommended volume by manufacturer, balloon transmural pressure was <-1 cmH2O in 71% and 53% of cases, it was negatively related to chamber pressure (rho=-0.97 and -0.71; P<0.0001) and reached values of -10.4 (-12.4, -9.7) and -9.8 (-10.6, -3.4) at 30 cmH2O. CONCLUSION: Measuring positive esophageal pressures needs higher injected volumes than usually recommended. The range of appropriate filling volumes is catheter-specific. Both absolute values and respiratory changes of esophageal pressure can be underestimated by an underfilled balloon.

Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche.

Effects of oral glucose administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH release in children and adults.

It has been suggested that hypothalamic regulation of GH secretion in children may differ from that in adults. On the other hand, there is evidence that oral glucose administration affects GH secretion through hypothalamic mechanisms. Therefore, we investigated spontaneous and GHRH-stimulated (1 microgram/kg BW) GH responses after oral glucose administration (children, 1.75 g/kg BW; adults, 75 g) in peripubertal normal children (13 girls and 13 boys, aged 11.7 +/- 0.4 yr; range, 8-13) and healthy adults (12 males and 14 females, aged 25.7 +/- 1.2 yr; range, 18-39). Three studies were carried out. In study 1, serum GH levels in 8 children were suppressed (< 1 microgram/L) for 135 min after oral glucose administration. Afterward, there was a rise in serum GH levels. In 8 adults, the suppressive effect of glucose persisted throughout the 210-min study period, and no GH rebound appeared. In study 2, the GH responses to iv GHRH boli in 10 adults and 10 children were, respectively, inhibited, unchanged, or augmented by an oral glucose load administered 30, 60, or 120 min before GHRH challenge. In study 3, oral glucose administration to 8 adults greatly enhanced the GH response to GHRH given 180 min after the glucose, whereas in 8 children, the GH response to GHRH was unchanged. In conclusion, glucose affects basal and GHRH-stimulated GH release in a similar manner in adults and children, indicating that neuroregulatory influences of glucose on the GH axis may not differ in the two age groups. In children, however, the duration of both the initial inhibitory and subsequent stimulatory effects of glucose administration on GH secretion is shorter.

A comparison of two GM-CSF schedules to counteract the granulo-monocytopenia of carboplatin-etoposide chemotherapy.

In order to obtain the beneficial effects from granulocyte-macrophage colony-stimulating factor (GM-CSF) on granulo-monocyte recovery with the minimum dose and toxicity, we compared the effect of two different GM-CSF schedules (5 micrograms/kg/day subcutaneously, days 5 to > 18 versus days 12 to > 18 on the cytopenias which follow cytostatic treatment with carboplatin (400 mg/m2 intravenous (i.v.) day 1) and etoposide (100 mg/m2 i.v. days 1 to > 3). 13 patients entered the study for a total of 36 evaluable cycles. The cytostatic treatment produced a neutropenia that persisted for up to day 22 (absolute neutrophil count (ANC) < 1000/microliters in 25% and ANC < 2000 in 50% of control cycles). Early GM-CSF administration markedly increased the leucocyte nadir and produced two waves of leucocytosis: an early one, linked to marrow reserve release and presumably of no value to the patients; and a delayed one, due to marrow precursor and progenitor cell proliferation, in which the granulomonocytosis was associated with a marked eosinophilia. The delayed GM-CSF administration markedly increased the leucocyte nadir and accelerated granulo-monocyte recovery (with an only modest eosinophilia), so that chemotherapy could be repeated every 21 days in all the patients.

Opioid peptides do not modulate atrial natriuretic peptide or aldosterone release under basal conditions in man.

The effect of two analogues of [Met]-enkephalin, [D-Ala2,N-Phe4,Met(0)-ol5]-enkephalin and its guanyl derivative, on plasma concentrations of atrial natriuretic peptide (ANP) and serum aldosterone in six normal subjects was investigated. All subjects were given a 1 litre water load to inhibit vasopressin release. Both analogues, when injected i.v. at a dose of 100 micrograms, stimulated release of prolactin and GH and inhibited serum cortisol; there was no significant change in blood pressure, pulse rate or urine output. Neither plasma concentrations of ANP nor serum aldosterone levels changed significantly after injection of either analogue at a low or high dose. Naloxone, given i.v. as an 8 mg bolus, also failed to alter concentrations of either ANP or aldosterone, while it significantly stimulated the release of serum LH and cortisol. It was concluded that under basal conditions opiate receptors are unable to modulate plasma ANP or serum aldosterone concentrations.