bluuebunny/crossref_metadata_2025 huggingface dataset:
Body Stalk Anomaly Diagnosed in the 2nd Trimester
Authors: Daskalakis George , Pilalis Athanasios , Papadopoulos Demetrios , Antsaklis Aris
Published: August 2003

We examined a 20-year-old primigravida by ultrasound at 21 weeks of gestation during routine anomaly scanning. Several fetal deformities were demonstrated: the upper part of the body was in the amniotic cavity, while the lower part was in the celomic cavity. A large abdominal wall defect was detected with herniation of the liver and the intestine. The limbs were deformed, the spine had severe kyphoscoliosis, and the umbilical cord was very short. These findings were suggestive of a body stalk anomaly. Termination of the pregnancy was offered and decided by the parents. The pathology report confirmed the ultrasonographic diagnosis.
Do Microbiological Factors Account for Poor Pregnancy Outcome among Unmarried Pregnant Women in Poland?
Authors: Kalinka Jarosław , Laudański Tadeusz , Hanke Wojciech , Wasiela Małgorzata
Published: August 2003

Objective: Being unmarried is a well-known risk factor for poor pregnancy outcome such as preterm delivery and intrauterine growth restriction. The aim of this prospective study was to assess the prevalence and risk of bacterial vaginosis (BV) and selected bacteria isolated from the lower genital tract and to determine the socioeconomic and microbiological characteristics that might be responsible for poor pregnancy outcome observed among unmarried pregnant women. Methods: The study population comprised 196 pregnant women attending 10 randomly selected outpatient maternity units in the Lodz region, central Poland. Cervicovaginal samples were obtained between 8 and 16 weeks of gestation. Based on Spiegel’s criteria, gram-stained vaginal smears were examined for BV and the BV-associated flora was sought by culture. To evaluate the risk factors, relative risk ratios were calculated using EPI INFO software. Results: Among 196 pregnant women, 40 (20.4%) were unmarried. BV was diagnosed among 55 (28.1%) women studied.In the univariate analysis, unmarried pregnant women were characterized by younger age, primary educational level, poor economic situation and excessive smoking during pregnancy, as compared to married women. The unmarried status was a borderline risk factor for BV (OR = 1.83, 95% CI 0.94–4.9) after adjustment for age, smoking and education. An analysis of the microbiological culture from the lower genital tract revealed that unmarried pregnant women had a higher risk for several types of pathological microflora, as compared to married women. However, this finding was significant only for Mycoplasma hominis. The independent risk factors of M. hominis were the young age of the subject and a low concentration of Lactobacillus spp. Conclusions: The observed socioeconomic, demographic and microbiological differences between unmarried and married women could be responsible for the poor pregnancy outcome among unmarried pregnant women in Poland. Unmarried pregnant women should be covered by comprehensive medical care even before pregnancy.Further studies taking into account the role of psychological stress, patterns of sexual behavior and substance abuse during pregnancy could help identify the factors responsible for adverse pregnancy outcome among unmarried pregnant women.
Postmortem Validation of Imaging-Derived Formulas for Prediction of Fetal Lung Volume
Authors: De Paepe Monique E. , Carr Stephen R. , Cassese John A.
Published: August 2003

Objective: To determine the validity of existing imaging-derived formulas for predicting the fetal lung volume (FLV). Methods: In a consecutive series of postmortem lungs without pulmonary anomalies, the observed FLV (FLVobs) after inflation was correlated with individual fetal variables used in imaging-derived formulas. In addition, FLVobs was correlated with the predicted FLV calculated according to these same formulas. Results: Postmortem FLVobs showed a strong correlation with estimated fetal body weight, biparietal diameter, and head circumference (r > 0.9). The correlation of FLVobs with gestational age, femur length, and liver weight was less strong (0.8 < r < 0.9). The correlation was strongest for midgestation fetuses (between 22 and 32 weeks’ gestation). The predicted FLV calculated using formulas based on fetal body weight, biparietal diameter, and head circumference showed the strongest correlation with the actual FLVobs (r > 0.9). Conclusions: Postmortem FLVobs strongly correlates with fetal body weight, biparietal diameter, and head circumference, especially in midgestation fetuses. Regression formulas based on these fetal variables provide the most accurate prediction of FLV.
Effect of α-Fetoprotein and Derived Peptides on Insulin- and Estrogen-Induced Fetotoxicity
Authors: Butterstein George , Morrison Jennifer , Mizejewski G.J.
Published: August 2003

Both insulin and estrogen are well recognized as growth-promoting substances at physiological concentrations, but they function as teratogens at high doses. Both agents can affect alterations in fetal and maternal serum human α-fetoprotein (HAFP) levels during pregnancy. In the present study, we have employed animal models of both insulin and estrogen fetotoxicity and teratogenicity in order to study the growth-regulatory properties of HAFP and its derived peptides (HAFP/PEP). We report here the effects of HAFP/PEP on fetotoxicity, congenital malformations, and growth retardation in developing chick and murine fetuses. In the insulin model, HAFP/PEP were effective in reducing both fetal mortality and anatomic anomalies, with the result that growth-retarded fetuses were produced. With HAFP/PEP treatment, fetal demise was reduced by as much as 73 and 63% in murine and chick fetuses, respectively, while fetal anomalies were diminished by 50% during chick development. Genebank searches of identity/similarity in a HAFP/PEP fragment identified matches with a number of proteins associated with glucose, pH, ionic, osmotic, and oxidative stresses, and with heat shock, in addition to stress proteins related to protein folding/unfolding processes. It was proposed that the peptide segment on HAFP may represent a topographic ‘hotspot’, sensitive to stress/shock conditions, which exhibits a propensity for conformational alteration in the tertiary structure of the fetal protein.
Evaluation of Prolonged Fetal Monitoring with Normal and Pathologic Outcome Probabilities Determined by Artificial Neural Network
Authors: Maeda Kazuo , Noguchi Yasuaki , Matsumoto Fujihiko
Published: August 2003

Objective: The purpose of this study was to objectively evaluate prolonged fetal heart rate (FHR) monitoring, which has been difficult to do with conventional cardiotocogram (CTG). Methods: FHR was analyzed by an artificial neural network computer that calculates probabilities of normal, pathologic and suspicious outcome. Earlier normal and pathologic outcome probabilities (OPs) recorded during 15-min intervals are averaged every 5 min. Initially, two curves (the averaged normal and pathologic OPs) are compared. Furthermore, a single curve traced for each difference between the averaged normal and pathologic OPs and its value are studied. Our FHR probability data are of 9 cases reported in a previous paper on neural network FHR analysis. Results: In the 4 cases of normal neonatal condition, the trends of the averaged curves and the last averaged values were higher for normal OP than for pathologic OP, and the final values of the difference were >0. On the other hand, in the 5 cases of neonatal depression, the trend of the two curves and the final values were lower for normal than for pathologic OP; and the final difference values of averaged probabilities were <0. For prolonged monitoring, the single parameter is more useful than the comparison of the two curves. Conclusion: A useful single parameter is obtained for the accurate and objective evaluation of prolonged FHR monitoring. The present method is promising for prospective studies using the combined system of experts and neural computers.
Studies on the Isolation and Identification of Fetal Nucleated Red Blood Cells in the Circulation of Pregnant Women before and after Chorion Villus Sampling
Authors: Christensen B. , Kølvraa S. , Lykke-Hansen L. , Lörch T. , Gohel D. , Smidt-Jensen S. , Bang J. , Philip J.
Published: August 2003

Objective: To investigate the feasibility of various molecular forms of hemoglobin as markers for fetal nucleated red blood cells (NRBCs). Methods: The presence of epsilon and gamma globin positive NRBCs was investigated in pure fetal blood and in blood from pregnant women before and after chorion biopsy. Maternal samples were enriched for NRBCs by various conventional methods, including limited enrichment by only positive CD71 selection or single density gradient. We searched for fetal cells on slides by automated scanning. Fetal cells were defined by (1) the presence of epsilon or gamma globin and (2) simultaneously by the presence of a Y chromosome signal. Results: 18 of 25 gamma globin positive cells identified in blood samples after chorion biopsy were chromosome Y signal positive, and 1 cell had two X chromosome signals. 263 of 339 epsilon globin positive cells identified in blood samples after chorion biopsy were hybridized with X and Y chromosome probes. None had two X signals, and 249 were Y positive. In blood samples before chorion biopsy, only 1 epsilon globin positive fetal NRBC and no epsilon globin positive maternal NRBCs were found. Conclusions: Epsilon globin may be specific for fetal NRBCs. Only 1 epsilon globin positive fetal cell was identified in 1 of 12 blood samples before chorion biopsy, representing a total of 182 ml of maternal blood. This suggests that most fetal cells found in maternal blood by fluorescence in situ hybridization methods may not be NRBCs.
Percutaneous Ultrasound-Guided Injection of the Trachea in Fetal Sheep: A Novel Technique to Target the Fetal Airways
Authors: David A.L. , Peebles D.M. , Gregory L. , Themis M. , Cook T. , Coutelle C. , Rodeck C.H.
Published: August 2003

Objective: To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep. Methods: Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.5–0.8 term, n = 18) fetal sheep using ultrasound guidance. Results: Injection of the trachea in the fetal thorax was successful in 16 out of 18 fetuses and achieved at the first attempt in 9 fetuses within 12 min [mean 7 min and 31 s ± (SD) 3 min and 4 s]. Survival was 100%. Injecting the trachea in the neck was less successful. Conclusions: The fetal trachea of the sheep can be safely accessed by percutaneous ultrasound-guided injection to deliver vectors directly to the fetal airways for gene therapy. It may also enable tracheal occlusion for the antenatal treatment of congenital diaphragmatic hernia without the need for endoscopy or open surgery.
Non-Viable Cervico-Isthmic Pregnancy: The Importance of an Accurate Sonographic Diagnosis to Preserve Fertility
Authors: Loureiro Teresa , Cunha Manuela , Marques Eduarda , Araújo Maria Libânia , Montenegro Nuno , Laurini Ricardo , Exposito Maria Isabel , del Pilar Martinez Maria
Published: August 2003

Background: Cervico-isthmic pregnancy is a rare occurrence and until the use of current ultrasonographic techniques was associated with a disastrous outcome for women desiring to maintain their fertility. Case Report: A 39-year-old woman was diagnosed at 12 weeks of amenorrhoea with an intra-uterine non-viable pregnancy and a low implantation of the gestational sac. Medical management of this situation with a regimen of intravaginal misoprostol was unsuccessful. At introduction of a cervical expander severe vaginal bleeding ensued, leading to an emergency curettage followed by a life-saving hysterectomy. Pathologic examination confirmed the peroperative impression of an isthmic implantation of the gestational sac. Conclusion: Early ultrasonographic diagnosis is essential to make conservative management of cervico-isthmic pregnancy possible.
Fas Ligand Expression in the Organ of Corti
Authors: Bodmer Daniel , Brors Dominik , Bodmer Morana , Pak Kwang , Ryan Allen F.
Published: August 2003

We have previously demonstrated by FACS analysis and histochemistry that Fas ligand (FasL) increases on cochlear cell surfaces after immune response or stimulation with γ-interferon (IFN-γ). To determine whether the appearance of FasL on cochlear cell membranes is related to gene expression or to posttranslational events, cochlear cells were treated with IFN-γ. They were evaluated for FasL gene expression by real-time PCR and for FasL protein localization by confocal microscopy of permeabilized and immunolabeled cells. Real-time PCR analysis of cDNAs generated from unstimulated or IFN-γ-stimulated organ of Corti demonstrated no change in the transcription of the gene encoding FasL. In contrast, confocal microscopy revealed dramatic changes in the cellular distribution of FasL, consistent with movement from the endoplasmic reticulum to the cytoplasm and cell membrane. The results suggest that recruitment of preformed FasL from intracellular compartments, rather than its biosynthesis, is responsible for the increase in FasL on the cell surface following IFN-γ stimulation. This is similar to the response of cytotoxic T lymphocytes in which gene expression is not involved in FasL surface appearance. Presumably, the use of preformed FasL increases the rapidity of this response. FasL localization to the membrane may be involved in protecting the inner ear from autoimmunity or inflammation. Alternatively it may be related to cochlear cell death in response to inflammatory stress.
Crossed and Uncrossed Olivocochlear Pathways Exacerbate Temporary Shifts in Hearing Sensitivity after Narrow Band Sound Trauma in Normal Ears of Animals with Unilateral Hearing Impairment
Authors: Rajan R.
Published: August 2003

Olivocochlear (OC) pathways have been shown to reduce the temporary threshold shifts (TTSs) caused by traumatic sounds. More recently they have been shown to exacerbate TTSs under certain conditions. One condition is the normal-hearing ear of animals with a chronic unilateral hearing loss. Testing with pure tone trauma showed that then (a) the normal-hearing ear had a lower-than-normal ‘intrinsic’ susceptibility to intense tones, (b) binaural trauma exacerbated TTSs in the normal-hearing ear through the activity of uncrossed OC (UOC) pathways, and (c) there was no effect on TTSs of the crossed OC (COC) pathway to the normal-hearing ear. The present study is an examination in such animals of effects with noise band trauma. The effects here confirm the previous finding that under such conditions the normal-hearing ear has a lower-than-normal susceptibility to loud sound, and binaural loud sounds exacerbate TTSs in the normal-hearing ear. They extend the previous study by demonstrating that with this traumatic sound, both COC and UOC pathways exacerbate TTSs. These effects contrast against the effects seen in animals with bilaterally normal hearing for the same noise band. Given the commonality of unilateral hearing losses in the normal human population, these data have implications for the functional effects of the OC pathways on loud sound-induced hearing damage.
Language and Speech Perception Outcomes in Hearing-Impaired Children with and without Connexin 26 Mutations
Authors: Dahl Hans-Henrik M. , Wake Melissa , Sarant Julia , Poulakis Zeffie , Siemering Kirby , Blamey Peter
Published: August 2003

This study addressed the question of whether a hearing loss caused by mutations in the connexin 26 gene had a significant effect on language and speech perception outcomes in children using cochlear implants or hearing aids. The families of children who had participated in two previous studies of language development were invited to participate in this genetic study. From the 52 children whose families agreed to participate, 15 children with connexin 26 mutations in both chromosomes were identified. After taking into account other factors which are known to affect language development and speech perception in children with impaired hearing, no significant differences were found between the 15 children where connexin 26 was known to be the cause of deafness and the other 37 children in the study.
Improvements in Trunk Sway Observed for Stance and Gait Tasks during Recovery from an Acute Unilateral Peripheral Vestibular Deficit
Authors: Allum John H.J. , Adkin Allan L.
Published: August 2003

Objectives: Our aim was to track improvements in postural control during recovery from an acute unilateral peripheral vestibular deficit (UVL), presumably due to vestibular neuritis, and to determine if recovery rates were different for stance and gait tasks. Postural control was quantified using simple measurements of trunk sway: amplitudes of trunk sway angle and angular velocity, in the roll and pitch directions as well as task duration, were examined for a battery of stance and gait tasks. These measures were collected at the onset of the deficit and then 3 weeks and 3 months later. Study Design: A repeated-measures design was used for UVL subjects and age-matched healthy controls. Stance tasks involved standing on 1 or 2 legs with eyes open or closed. Gait tasks consisted of tandem gait, walking normally with eyes closed, or with the head rotating or head pitching, walking up and down stairs and walking over a series of low barriers. Stance and tandem gait tasks were repeated using a foam support surface instead of a normal floor. Patients: Twenty-eight patients with acute UVL were examined. Main Outcome Measures: The range of trunk sway angular displacement and angular velocity in the pitch and roll directions was measured for each task in addition to task duration. The measures were compared with those of normal subjects. Results: The amplitudes of pitch trunk sway for 2-legged stance tasks with eyes closed underwent the greatest reduction 3 weeks after UVL onset. At 3 months, trunk sway was almost normal for all 2-legged stance tasks. One-legged stance tasks with eyes open showed a similar but slower improvement. Stance time without a fall showed a very rapid improvement for 1-legged tasks but was still shorter than that of normal subjects at 3 months. Trunk sway for the simple gait tasks was within normal range at 3 months; however, task duration was still longer than normal. More complex gait tasks, such as walking 8 tandem steps on foam or walking up and down stairs, showed no improvement in trunk roll sway at 3 months. A mix of variables from mainly gait tasks best identified a balance deficit due to UVL, with complex gait tasks becoming more important for identification purposes as compensation progressed. The accuracy of UVL identification with durations alone was 75% of the accuracy with combined trunk sway and duration measures. Conclusions: These data suggest that recovery of normal trunk control during the compensation process for unilateral vestibular hypofunction is more rapid for stance tasks than gait tasks. Even at 3 months, trunk sway for complex gait tasks was not normal. Thus, trunk sway for gait tasks provides a better insight into remaining deficits in balance control of vestibular-loss patients than the sway of stance tasks.
Acoustic and Electrical Pattern Analysis of Consonant Perceptual Cues Used by Cochlear Implant Users
Authors: Teoh Su Wooi , Neuburger Heidi S. , Svirsky Mario A.
Published: August 2003

It is hypothesized that for postlingually deafened adult cochlear implant (CI) users, a significant source of their perceptual performance variability is attributable to differences in their ability to discriminate the basic perceptual cues that are important in speech recognition. Previous research on ‘electric hearing’ has identified consistent perceptual cues for vowel recognition. However, the results on consonant perception by CI users are less clear. The primary purpose of this study is to present a quantitative method of evaluating potential ‘electric cues’ used by CI users in consonant identification. Since the actual input signals to the auditory periphery of CI users are electric in nature, we elected to measure the CI electric discharge patterns in addition to the original acoustic waveforms. The characteristics of the electric discharge patterns in response to intervocalic consonants were quantified and correlated with the dimensions of CI patients’ perceptual spaces, which were computed from multidimensional scaling analyses of their consonant confusion matrices. The results agree with most, but not all, commonly accepted acoustic cues used by normal-hearing listeners. The correlation findings also suggest that CI users employ different sets of ‘electric cues’ in perceiving consonants that differ in their manner of articulation. Specifically, spectral and temporal cues associated with slowly changing formant structures and transitions, and features associated with frication and high-frequency noise, are all highly correlated with the perceptual dimensions of all CI users. However, rapidly changing formant transitions, such as those present in stop consonants, did not appear to play a significant role in consonant recognition by more poorly performing CI subjects. The perceptual results were consistent with our physical findings that the SPEAK coding strategy partially degraded the rapidly changing formant transitions.
Helical CT Scanning in the Diagnosis of Pulmonary Embolism
Authors: Garg Kavita , Macey Loren
Published: August 2003

CT pulmonary angiography has become the screening exam of choice to evaluate for pulmonary embolism (PE), especially in subjects with an abnormal chest radiograph. A good-quality CT pulmonary angiogram has a high accuracy rate for the evaluation of PE. Investigators have reported that subsegmental emboli can be missed; however, visualization of smaller arterial branches and, therefore, detection of small emboli have improved with the availability of multidetector scanners. Some of the advantages of using CT for PE compared to lung scintigraphy include: (1) direct visualization of emboli on CT; (2), evaluation of lung parenchyma and mediastinum (this may provide an alternate diagnosis); (3) capability to acquire a CT venogram without additional contrast with ‘one-stop examination’ for the evaluation of thromboembolic disease.
Effects of Inhaled Corticosteroids with Different Lung Deposition on Exhaled Hydrogen Peroxide in Stable COPD Patients
Authors: van Beurden W.J.C. , Harff G.A. , Dekhuijzen P.N.R. , van der Poel-Smet S.M. , Smeenk F.W.J.M.
Published: August 2003

Background: The effects of inhaled corticosteroids (ICS) on markers of oxidative stress in patients with stable COPD are unclear. Objectives: The aim was to investigate the effect of ICS on exhaled H2O2 in stable COPD patients and to compare ICS with different lung deposition. Methods: Forty-one stable patients with moderate COPD (FEV1 ∼60% predicted) were randomized to sequence 1; first HFA-134a beclomethasone dipropionate (HFA-BDP, an ICS with more peripheral deposition) 400 µg b.i.d., then fluticasone propionate (FP, an ICS with more central deposition) 375 µg b.i.d. (n = 20) or sequence 2 ; first FP, then HFA-BDP (n = 21). Both 4-week treatment periods were preceded by a 4-week washout period. After each period, the concentration of H2O2 in exhaled breath condensate was measured. Results: The H2O2 concentration decreased significantly after the first treatment period in both sequence 1 and 2 (p < 0.05, p = 0.01, respectively). In neither sequence was there a return to baseline values after the second washout, indicating a carry-over effect. The concentrations remained low in both sequences during the second treatment period. Conclusions: Both ICS appeared to reduce exhaled H2O2 in stable COPD patients. However, this study showed no difference between ICS with different deposition patterns, which in part may be due to the carry-over effect.
Effect of Zafirlukast on Methacholine and Ultrasonically Nebulized Distilled Water Challenge in Patients with Mild Asthma
Authors: Carratù P. , Morelli N. , Freire A.X. , Pugazhenthi M. , Guerra S. , Umberger R. , Allegra L.
Published: August 2003

Background: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). Objective: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. Methods: Fourteen non-atopic patients (8 males, 20–42 years, forced expiratory volume in 1 s (FEV1) 97% SD ± 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. Results: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV1 drop –10.75% SD ± 1.89, p < 0.001) and UNDW induced (maximum FEV1 drop –12% SD ± 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV1 drop following MC (maximum FEV1 drop –33.22% SD ± 1.42, p < 0.001) and UNDW challenge (maximum FEV1 drop –30.02% SD ± 0.4, p < 0.001). Conclusions: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.
Expression and Release of Interleukin-8 by Human Bronchial Epithelial Cells from Patients with Chronic Obstructive Pulmonary Disease, Smokers, and Never-Smokers
Authors: Schulz Christian , Wolf Konrad , Harth Martina , Krätzel Kirsten , Kunz-Schughart Leoni , Pfeifer Michael
Published: August 2003

Background: One of the consistently observed features in chronic obstructive pulmonary disease (COPD) are markedly increased neutrophils in the airways which are accompanied by increased levels of interleukin-8 (IL-8) in induced sputum and bronchoalveolar lavage fluid. To some extent, IL-8 may derive from bronchial epithelial cells since airway epithelium plays a crucial role in initiating and augmenting host defense mechanisms. Objectives: We hypothesized that a marked increase in bronchoepithelial IL-8 expression and release may be found in the airway epithelium of COPD patients compared to ‘healthy’ smokers and never-smokers. Methods: Primary bronchoepithelial cell cultures from COPD patients, smokers, and never-smokers were established. The unstimulated and TNFα-induced IL-8 release was measured by enzyme-linked immunosorbent assay. In addition, mRNA expression levels were quantified by means of reverse transcriptase polymerase chain reaction and light cycler measurements. Results: In subjects with COPD the constitutive and stimulated IL-8 release was significantly higher compared to ‘healthy’ smokers and control subjects, whereas no differences were seen between smokers and the control group. Quantitative assessment of transcript levels confirmed these data, displaying significantly higher mRNA levels in primary bronchial epithelial cells from COPD patients compared to controls (p < 0.05) in uninduced and stimulated conditions (p < 0.05). Conclusions: These results suggest that patients with chronic obstructive airflow limitation are characterized by a significant upregulation of bronchial epithelial IL-8 expression levels and secretion, indicating specific differences in epithelial cell activation in COPD patients compared to smokers and control subjects.
Systemic Immune Cell Activation in a Subgroup of Patients with Idiopathic Pulmonary Fibrosis
Authors: Homolka Jiri , Ziegenhagen Manfred W. , Gaede Karoline I. , Entzian Peter , Zissel Gernot , Müller-Quernheim Joachim
Published: August 2003

Background: The prognosis of idiopathic pulmonary fibrosis (IPF/UIP) is poor and its immunopathogenesis is insufficiently understood. Objectives: The aim of our study was to elucidate the compartmentalization of cell activation and the influence of corticosteroid therapy upon this activation in IPF/UIP. We determined the concentrations of proinflammatory cytokines released by bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMNC) in treated and untreated patients with IPF/UIP. We chose tumor necrosis factor-α (TNFα) since it is a cytokine predominantly secreted by cells of the monocyte/macrophage lineage and interleukin-2 (IL-2) exclusively by T lymphocytes. Methods: The release of TNFα and IL-2 by BAL cells and PBMNC was measured in cell culture supernatants of 72 treated and untreated IPF/UIP patients. Additionally, in the blood compartment serological parameters reflecting the monocyte/macrophage and lymphocyte activation, such as neopterin and soluble IL-2 receptor (sIL-2R), were determined. Results: The TNFα release by BAL cells was significantly elevated in both groups compared to controls but did not differ between treated and untreated patients with IPF/UIP. In 7 of 19 untreated patients with IPF, PBMNC were activated and released increased amounts of TNFα. In only 1 of 17 treated patients with IPF, TNFα release by PBMNC could be found. The serum level of neopterin, a marker of cell activation of the monocyte/macrophage lineage did not differ between treated and untreated patients. The BAL lymphocyte and PBMNC IL-2 release was significantly elevated in IPF/UIP patients without therapy compared to controls (p < 0.05). In contrast, no IL-2 release of BAL cells or PBMNC was observed in treated IPF/UIP patients. Lymphocyte activation was furthermore identified in untreated IPF patients by elevated soluble IL-2 receptor serum concentrations (p < 0.0001). Conclusions: Cells of the monocyte/macrophage lineage and T lymphocytes are activated in BAL cells and PBMNC of patients with IPF/UIP. During treatment, the systemic and local activation of T cells is suppressed. BAL macrophages, however, maintain their activated status, which might be the cause for the frequent chronic progression of the disease.
Tumour Necrosis Factor-α in Comparison to Adenosine Deaminase in Tuberculous Pleuritis
Authors: Tahhan Metin , Ugurman Feza , Gozu Ayse , Akkalyoncu Behiye , Samurkasoglu Belgin
Published: August 2003

Background: Adenosine deaminase (ADA) is already used for the differential diagnosis of tuberculosis pleurisy. Tumour necrosis factor-α (TNF) is another marker which has been investigated for this purpose. Objective: We evaluated the diagnostic value of pleural fluid and serum TNF concentrations in tuberculous pleuritis and compared them to ADA. Methods: Sixty-two patients (24 tuberculous pleuritis, 38 non-tuberculous pleuritis) with exudative pleurisy were included. Serum and pleural fluid TNF concentrations were determined in all patients and ADA activity in 54 patients. Pleural fluid TNF concentrations and pleural fluid/serum TNF were compared to pleural fluid ADA activity and pleural fluid/serum ADA. Results: When the tuberculous and non-tuberculous groups were compared, pleural fluid TNF concentrations (65.4 ± 136.9 pg/ml vs. 54.5 ± 144.2 pg/ml, respectively; p < 0.001), pleural fluid ADA activity (74.2 ± 33.3 U/l vs. 23 ± 16.3 U/l; p < 0.0001), pleural fluid/serum TNF (2.55 ± 5.23 vs. 0.26 ± 0.2; p < 0.001) and pleural fluid/serum ADA (4.58 ± 8.14 vs. 1.15 ± 0.7; p < 0.0001) were significantly higher in the tuberculous group. When cut-off points were assessed, 8 pg/ml and 40 U/l were found for pleural fluid TNF concentrations and pleural fluid ADA activity, respectively. Sensitivity, specificity, area under the curve were 87.5%, 76.3%, 0.772 for pleural fluid TNF concentrations and 90.9%, 89.5%, 0.952 for pleural fluid ADA activity, respectively; the difference between these areas under the curves was significant (p < 0.05). Conclusions: Pleural fluid TNF levels and pleural fluid/serum TNF were higher in tuberculous effusions than in other exudates, but their diagnostic value appears to be poorer than that of ADA.
Effects of Almitrine Bismesylate on Arterial Blood Gases in Patients with Chronic Obstructive Pulmonary Disease and Moderate Hypoxaemia: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Study
Authors: Górecka D. , Śliwiński P. , Pałasiewicz G. , Pachocki R. , Zieliński J.
Published: August 2003

Background: Advanced chronic obstructive pulmonary disease (COPD) generates high costs, especially when patients require domiciliary long-term oxygen therapy (LTOT). Almitrine bismesylate has been shown to improve gas exchange in the lungs. Our hypothesis was that long-term treatment with almitrine might postpone the prescription of LTOT. Objective: To evaluate the effects of almitrine sequential treatment on arterial blood gases in COPD patients with moderate hypoxaemia. Methods: COPD patients with moderate hypoxaemia [partial oxygen tension in arterialised blood (PaO2) between 7.33 and 8.66 kPa (56–65 mm Hg)] were investigated. After a 1-month run-in period, patients were given either almitrine 100 mg per day or placebo for sequential treatment for a total of 12 months. Results: 115 patients in a steady state (57 in the almitrine and 58 in the placebo group) were included. Mean age was 60 years, mean forced expiratory volume in 1 s was 34 ± 13% of predicted and mean PaO2 was 8.04 ± 0.5 kPa (60.5 ± 3.8 mm Hg). 38 patients were lost to follow-up, 23 in the almitrine and 15 in the placebo group. The majority of drop-outs were due to adverse events (AE; 16 in the almitrine and 9 in the placebo group). Almitrine treatment resulted in PaO2 improvement of 0.43 ± 0.88 kPa (3.2 ± 6.6 mm Hg) (p = 0.003). The treatment effect between almitrine and placebo was 0.45 kPa (3.4 mm Hg) (p = 0.003). In the almitrine group, two distinct subgroups were observed: responders (n = 19) and non-responders (n = 38). Almitrine treatment in responders resulted in a clinically significant improvement in PaO2 of 1.36 ± 0.7 kPa (10.2 ± 5.3 mm Hg) (p < 0.0001) and a reduction of partial carbon dioxide tension in arterialised blood. 31 patients experienced serious AE: 17 in the almitrine and 14 in the placebo group. Five patients died during the study (3 in the almitrine and 2 in the placebo group). Most AE occurring during the study were related to underlying disease. Clinical diagnosis of polyneuropathy resulted in the withdrawal of 5 patients in the almitrine group and 3 patients in the placebo group. Four patients in the almitrine group experienced weight loss. Conclusions: Almitrine treatment of patients with severe COPD and moderate hypoxaemia resulted in a small but significant improvement in PaO2 over 12 months. A clinically important improvement in gas exchange was observed in 33% of treated patients. These patients may be candidates for long-term treatment.
Cytokine mRNA Expression in Isocyanate-Induced Hypersensitivity Pneumonitis
Authors: Sumi Yuki , Kyi Min , Miyazaki Yasunari , Ohtani Yoshio , Miyake Shuji , Yoshizawa Yasuyuki
Published: August 2003

Background: Diisocyanate is widely used as a polymerizing agent for manufacturing many products. However, repeated inhalation exposure to diisocyanates in the workplace can cause bronchial asthma, hypersensitivity pneumonitis (HP), and neoplasia. Objectives: In the current study, immunological tests were conducted to explore the mechanisms involved in the pathogenesis of diisocyanate-induced HP. Methods: Evaluations included 4 patients with diisocyanate-induced HP, 4 volunteers with current occupational exposure to diisocyanates and 4 normal volunteers without a history of exposure to diisocyanates. IgG and IgA antibody levels to diisocyanates were determined by ELISA in sera and BAL fluids. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or in the absence of 10 µg/ml MDI-HSA (4, 4′ diphenylmethane diisocyanate)-HSA (human serum albumin). 3H-thymidine uptake, mRNA expression by RT-PCR (beta-actin, IL-1beta, IL-2R, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta) were estimated. Results: Patients with diisocyanate-induced HP had detectable IgG and IgA antibodies to diisocyanates. In addition, PBMCs from HP patients proliferated in the presence of diisocyanates and showed enhanced expression of mRNA of proinflammatory cytokines. In contrast, normal volunteers with current occupational exposure showed elevated levels of mRNA expression of IL-10 and IL-2R, suggesting the presence of sensitized cells and protection from pathology as a result of enhanced IL-10 production. Conclusions: Patients with diisocyanate-induced HP are likely to override the protective effects of IL-10 as they express lower levels of this cytokine.
Endoscopic Transesophageal and Endoscopic Transbronchial Real-Time Ultrasound-Guided Biopsy
Authors: Krasnik Mark
Published: August 2003

The goal of preoperative staging of non-small-cell lung cancer is to identify patients who will benefit from surgical resection. Various imaging and less invasive modalities are now available to improve therapy decision-making, and with the introduction of multimodality treatment of lung cancer, proper staging of this disease is becoming more and more important. This staging process is therefore not only a question of determining the prognosis, but it is also necessary information for institution of the right treatment. Proper staging and restaging of lung cancer should also be a must in the evaluation of the different treatments of lung cancer in controlled clinical trials. In lung cancer, endoscopic ultrasound scanning (EUS) is emerging as an accurate, nonsurgical alternative to staging the mediastinum through EUS-fine-needle aspiration (EUS-FNA). The author presents publications on evaluating EUS in diagnosing lymph node involvement in lung cancer and tumor ingrowths in the mediastinum. With EUS it is possible to guide FNA with direct visualization of the needle path into the lymph nodes in real time. Although this method is only able to visualize the posterior path and the inferior parts of the mediastinum, it makes it possible to visualize the aortopulmonary window. The limitation of EUS is a sensitivity of about 90%; nonetheless, this method is more precise than other staging procedures except for mediastinoscopy, which is limited to only the anterior parts of the mediastinum.
Ultrasound Guidance for Medical Thoracoscopy: A Novel Approach
Authors: Hersh Craig P. , Feller-Kopman David , Wahidi Momen , Garland Robert , Herth Felix , Ernst Armin
Published: August 2003

Background: Commonly, a pneumothorax is induced before medical thoracoscopy to facilitate safe entry into the pleural space. Objective: Evaluate the use of transthoracic ultrasound to locate a safe entry site for trocar placement during medical thoracoscopy without induction of a preprocedure pneumothorax. Method: The study was designed as a prospective cohort study, performed in the setting of a tertiary care hospital with an active interventional pulmonology program. It included 20 consecutive patients referred for medical thoracoscopy. Results: Ultrasound identified entry sites in all 20 patients. All sites were successfully used, despite the presence of adhesions in 3 patients. There were no complications. Conclusions: Ultrasound could safely and reliably identify entry sites for trocar placement during medical thoracoscopy, even in patients with pleural adhesions. The use of ultrasound may replace the practice of pneumothorax induction before medical thoracoscopy.
Solitary Atypical Adenomatous Hyperplasia in the Lung of a 17-Year-Old Man with Spontaneous Pneumothorax
Authors: Shoji Tsuyoshi , Isowa Noritaka , Hasegawa Seiki , Li Mio , Morimoto Kojiro , Ueda Hiroyuki , Kitaichi Masanori , Manabe Toshiaki , Wada Hiromi
Published: August 2003

We report here a case of solitary atypical adenomatous hyperplasia (AAH). A 17-year-old non-smoker man developed spontaneous pneumothorax, and computed tomogram scanning of his chest revealed a ground-glass opacity measuring 5 × 5 mm in the right lung with no change in its size for the next 7 months. To exclude the possibility of pulmonary neoplasia, he underwent partial pulmonary resection. The postoperative pathologic diagnosis was AAH. The present case is very exceptional for AAH because of the patient’s young age and non-association with pulmonary carcinoma. The postoperative 23-month follow-up was uneventful.
Multiple Pulmonary Nodules in a Patient with Crohn’s Disease
Authors: Golpe Rafael , Mateos Alfonso , Pérez-Valcárcel Javier , Lapeña José A. , García-Figueiras Roberto , Blanco Joaquín
Published: August 2003

Crohn’s disease (CD) can be associated with respiratory involvement. Multiple pulmonary nodules are an infrequent finding in patients with CD. When they are found, histology usually shows sterile necrobiotic nodules, which are spherical aggregates of neutrophils, which frequently cavitate. We report a patient with inactive CD treated with mesalazine, who presented with multiple pulmonary nodules. Transthoracic biopsy of one of the nodules disclosed a benign, nongranulomatous inflammatory lymphoid infiltration. The radiographic abnormalities responded well to oral prednisone. Focal, nongranulomatous lymphoid infiltration thus must be considered in the differential diagnosis of multiple pulmonary nodules in patients with CD.
Acute Amiodarone-Induced Pulmonary Toxicity following Lung Resection
Authors: Handschin Alexander Edmund , Lardinois Didier , Schneiter Didier , Bloch Konrad , Weder Walter
Published: August 2003

Amiodarone-induced pulmonary toxicity has been described mostly in patients receiving large doses of the drug over prolonged periods. In this report, we describe the early onset of acute pulmonary toxicity leading to acute respiratory distress syndrome after a short course of amiodarone treatment following middle-lobe non-small-cell lung cancer resection.
The Wrong Stent at the Wrong Time: A Cautionary Tale
Authors: Noppen Marc , van Renterghem Dirk , Vanderstraeten Peter
Published: August 2003

Self-expandable metallic stents have been promoted for a multitude of indications because of their easy insertion and convenience. This may lead to inappropriate use. We report two patients in whom self-expandable metallic stents led to severe early or late complications. The correct choice of the type of a stent demands expertise with consideration and anticipation of late side effects especially in benign stenosis.
Sleep Apnea Syndrome in Endocrine Diseases
Authors: Bottini Paolo , Tantucci Claudio
Published: August 2003

It is increasingly recognized that sleep-disordered breathing (SDB) – from snoring to apnea-hypopnea syndrome (SAHS) – can affect patients with various endocrine diseases (ED). Different mechanisms are implied in SDB, promoting either central or, more frequently, obstructive apnea in different ED. In the past, acromegaly and hypothyroidism were first associated with both central and obstructive SAHS. Today, great attention is placed on the complex cause-effect relationship between diabetes mellitus and obstructive SAHS (and vice versa). Symptoms and signs of SAHS may complicate the clinical course of these diseases and should be promptly suspected to detect and possibly treat the accompanying SDB.
Topical Vaccination of DNA Antigens: Topical Delivery of DNA Antigens
Authors: Choi M.J. , Maibach H.I.
Published: August 2003

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune responses in vivo. The skin is an attractive site for the delivery of DNA antigens for DNA vaccination. However, due to skin’s barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability, chemical and physical approaches have been examined to decrease stratum corneum barrier properties. Topical vaccination has been achieved using topical application of naked DNA, DNA/liposomes or emulsion complex, liposomal cream, as well as physical methods such as stripping, electroporation, and micromechanical disruption methods. All methods resulted in a significant enhancement in humoral and cellular immune responses over naked DNA alone. To develop more cost-effective and needle-free vaccines, skin-targeted immunizations are required. This review focuses on the chemical and physical methods developed to enhance DNA delivery into skin.
Impact of Ultraviolet Radiation and Ozone on the Transepidermal Water Loss as a Function of Skin Temperature in Hairless Mice
Authors: Thiele J.J. , Dreher F. , Maibach H.I. , Packer L.
Published: August 2003

Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75–3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.
Mass Spectrometric Examinations of Stratum corneum Lipid Models Exposed to Ultraviolet Irradiation
Authors: Trommer H. , Plätzer M. , Wolf R. , Neubert R.H.H.
Published: August 2003

Lipid model systems consisting of the major components of the stratum corneum intercellular lipid matrix were studied to investigate the ultraviolet-radiation-mediated damage of these biomolecules. Pure lipids and liposomes were irradiated using a lamp emitting a solar radiation spectrum. The influences of the irradiation and the effects of added iron ions were studied by electrospray ionization mass spectrometry (MS) with an ion trap analyser. Exact mass measurements were carried out using a time-of-flight mass spectrometer. Only linolenic acid and cholesterol were found to be subject to oxidative changes caused by UV irradiation whereas the other lipids examined (dipalmitoylphosphatidylcholine, ceramide III and cholesterol sulphate) were stable to oxidative stress. Several lipid adducts were observed upon analysis of the liposomes. The composition of these adducts was identified by MS/MS experiments.