bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibronectin in Bronchoalveolar Lavage Fluid in Lung Cancer: Tumor or Inflammatory Marker?
Authors: Cremades M.J. , Menéndez R. , Rubio V. , Sanchis J.
Published: April 2003

Objective: To evaluate the potential value of the level of fibronectin (FN) in the bronchoalveolar lavage fluid (BALF) as a lung tumor marker. Method: We compare the results of determinations in the tumor-bearing and tumor-free lungs of 38 patients with lung cancer, in 19 patients with benign lung diseases and in 13 healthy control subjects. FN was determined in BALF by a competitive ELISA and was also measured in plasma with a nephelometric assay. FN levels in BALF are expressed also referred to total protein content (ng FN/mg TP). Results: The distribution of FN levels in BALF was not gaussian, and the levels in cancer patients were significantly greater than in healthy controls or in the contralateral lung. There was no significative difference in the levels in cancer compared with several benign conditions. In this study we observed a positive correlation between FN levels and total protein and polymorphonuclear leukocytes in BALF in the lung cancer and benign diseases group. Conclusion: These results do not support the possibility that FN levels in BALF were a general marker of lung cancer, and suggest that FN may mark the existence of pathologic lung processes associated with inflammation and, perhaps, tissue repair after bronchopulmonary injury.
Proinflammatory Cytokine Levels in Patients with Lung Cancer and Carcinomatous Pleurisy
Authors: Hoheisel Gerhard , Izbicki Gabriel , Roth Michael , Chan Christopher H.S. , Reichenberger Frank , Schauer Joachim , Perruchoud André P.
Published: April 2003

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 ± 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 ± 1,993 vs. 9,438 ± 1,407 pg/ml; p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 ± 176 vs. 10.2 ± 1.3 pg/ml, p < 0.0001; IL-8: 319 ± 85 vs. 9.6 ± 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 ± 1.3 pg/ml) in comparison to controls (7.3 ± 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 ± 1.5 pg/ml; all values are mean ± SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression or sIL-6R shedding in the presence of excessive amounts of IL-6.
Cavitary Pulmonary Metastases of Gallbladder Cancer
Authors: Baba Kenji , Hattori Tsutomu , Koishikawa Isao , Kamiya Tatsuo , Noda Aiji , Kobayashi Tadashi , Ikuta Koji
Published: April 2003

We report a case of multiple cavitary pulmonary metastases of gallbladder cancer. Radiologically, every cavity displayed a very thin wall containing only air inside. The postmortem histopathological examination showed that: (1) the cavities were surrounded by normal alveoli; (2) these walls were composed mostly of adenocarcinoma cells; (3) necrotic or mucous substance was sparse in the cavity space; (4) cancer cells infiltrated along the surface of the alveolar septa, and (5) the morphology of the cancer cells of the gallbladder and the lung was the same. It seemed likely that the thin-walled cavities in the lung might result from central breakdown of the tumor and subsequent expectoration of debris through the connected airways.
Local and Peripheral Plasma Endothelin-1 in Pulmonary Hypertension Secondary to Chronic Obstructive Pulmonary Disease
Authors: Çelik Gülfem , Karabiyikoglu Gülseren
Published: April 2003

Endothelin-1 (ET-1) has been described to have crucial effects in the initiation and evolution of pulmonary hypertension (PH) secondary to cardiac disorders. However, the precise role of ET-1 in PH induced by chronic obstructive pulmonary disease (COPD) is not yet clear. The objective of this cross-sectional study was to determine the local and peripheral plasma ET-1 profile of COPD patients with or without PH. Twenty-six COPD patients with clinical and/or laboratory findings suspicious of PH, and 20 healthy smoker volunteers constituted the study population. Patients were allocated to PH (n = 17) and non-PH (n = 9) groups according to their pulmonary artery pressures determined by right-heart catheterization. Plasma ET-1 samples, obtained from the main pulmonary artery (mixed venous blood) and peripheral blood (radial artery and brachial vein), were assessed by radioimmunoassay. Brachial vein ET-1 levels were within normal ranges in PH (2.7 ± 0.5 pg/ml) and non-PH (3.2 ± 0.7 pg/ml) COPD patients compared with that of the controls (4.4 ± 0.1 pg/ml). Likewise, radial artery ET-1 levels in PH (3.3 ± 0.7 pg/ml) and non-PH (2.9 ± 0.8 pg/ml) groups, and in controls (3.4 ± 1.1 pg/ml) were also comparable. The pulmonary artery ET-1 concentration of the PH group (13.6 ± 3.7 pg/ml) was higher than that of the non-PH group (2.2 ± 0.4 pg/ml) and that of the peripheral blood levels of controls. Elevated pulmonary artery ET-1 in the PH group was inversely correlated only with PaO2 levels. These results could be taken as an evidence of a local role of ET-1 in COPD-induced PH, but it remains to be clarified whether ET-1 is a marker or a mediator of PH in COPD.
Antiproliferative Properties of Human Alveolar Macrophages
Authors: Kessler Romain , Dumont Serge , Weitzenblum Emmanuel , Poindron Philippe
Published: April 2003

Objective: The aim of our study was to determine whether macrophages from lung cancer patients could acquire antitumoral properties in an in vitro model. Methods: We isolated macrophages from bronchoalveolar lavages performed in two groups of patients: patients with lung cancer and patients with lung infection. All patients were smokers. We used the inhibition of incorporation of 3H-thymidine by U937 tumoral cells as an in vitro cytostatic assay. Results: When stimulated by gamma interferon, alveolar macrophages either from lung cancer patients or from patients with lung infection induced cytostasis of proliferating U937 tumoral cells. This effect could be reproduced by using the supernatants of cultures of activated macrophages. When using optimal doses, gamma interferon showed an increased activity as compared with lipopolysaccharide. The combination of these two compounds was no more effective than gamma interferon alone in cancer patients. A macrophage/U937 tumoral cell ratio of 1/1 was sufficient to achieve a near-maximal cytostatic effect. Conclusions: Our results demonstrate that it is possible to activate, in vitro, alveolar macrophages from lung cancer patients by stimulation with gamma interferon. These macrophages acquire antiproliferative properties against a sensitive tumoral cell line.
Occupational Asthma due to Chromium
Authors: Leroyer C. , Dewitte J.D. , Bassanets A. , Boutoux M. , Daniel C. , Clavier J.
Published: April 2003

We describe a 28-year-old subject employed as a roofer in a construction company since the age of 19, who developed work-related symptoms of a cough, shortness of breath, wheezing, rhinitis and headaches. A description of a usual day at work suggested that the symptoms worsened while he was sawing corrugated fiber cement. Baseline spirometry was normal, and there was a mild bronchial hyperresponsiveness to carbachol. A skin patch test to chromium was negative. A specific inhalation challenge showed a boderline fall in forced expiratory volume in 1 s (FEV1) after exposure to fiber cement dust. Exposure to nebulization of potassium dichromate (K2Cr2O7), at 0.1 mg·ml–1 for 30 min, was followed by an immediate fall by 20% FEV1. Simultaneously, a significant increase in bronchial hyperresponsiveness was demonstrated.
Pharyngeal Cross-Sectional Area and Pharyngeal Compliance in Normal Males and Females
Authors: Huang J. , Shen H. , Takahashi M. , Fukunaga T. , Toga H. , Takahashi K. , Ohya N.
Published: April 2003

Obstructive sleep apnea syndrome is ascribed to pharyngeal dysfunction, but there are only a few reports about the normal morphological values in this anatomical region. We measured the pharyngeal cross-sectional area and the compliance (collapsibility), using the acoustic reflection technique with air breathing, in 181 healthy subjects (age 21–69 years). We assessed their sex-related differences, and the effects of age, body size and body postures on these parameters. The pharyngeal cross-sectional area, defined as the region from the fauces to the glottis, posturally changed with successive decreases in the sitting, left lateral decubitus and supine positions. The area was significantly greater in male than in female subjects in the sitting position (p < 0.01), but no difference was present in the recumbent positions. The pharyngeal cross-sectional area did not correlate with either age or body size. The specific pharyngeal compliance was greater in the males than in the females (p < 0.01) and increased with age only in the male subjects.
Oxygen Uptake and Cardiac Performance in Obese and Normal Subjects during Exercise
Authors: Salvadori A. , Fanari P. , Fontana M. , Buontempi L. , Saezza A. , Baudo S. , Miserocchi G. , Longhini E.
Published: April 2003

Work capacity and cardiopulmonary performance were studied in a group of 11 young obese subjects (BMI 39.9 kg/m2) and a group of 10 young normal subjects (BMI 22 kg/m2). First of all they underwent an incremental cycle ergometer test up to exhaustion. Subsequently, every subject of the two groups performed a constant work rate test at different work loads to estimate cardiac output (q̇) below anaerobic threshold (AT) by a 20-second CO2 rebreathing method. Obese subjects had a significantly lower AT (79 vs. 109 W). The ratio between oxygen uptake and heart rate (v̇O2/HR) (O2 pulse) was higher in the obese group; nevertheless, this variable became significantly lower if we took into consideration the ratio between O2 pulse and kilogram fat-free body mass or kilogram body weight. Both these observations suggest that their reduced work tolerance is linked with a reduced oxygen supply to the muscles in activity. q̇ increased in similar ways in obese and normal subjects at the preset work rates. The ratio q̇/body surface (cardiac index; CI) that we considered in order to try to minimize the differences in body sizes between the two groups, increased less in response to increasing work rates in our obese subjects than in normal subjects. As a whole, these data appear to be in line with a relatively less efficient cardiac performance during progressive work rates in obese subjects.
Nasopharyngeal Symptoms in Patients with Obstructive Sleep Apnea Syndrome
Authors: Brander P.E. , Soirinsuo M. , Lohela P.
Published: April 2003

Background: Nasal side effects are often reported during nasal continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea syndrome (OSAS) and may make the use of nasal CPAP difficult. Objective: The aim of this study was to evaluate the effect of nasal CPAP on nasopharyngeal symptoms in OSAS patients. Methods: The frequency and severity of nasopharyngeal symptoms and signs were prospectively evaluated in 49 consecutive OSAS patients (37 men, 12 women, mean (SD) age 54 (7) years, body mass index 35 (6) kg/m2) immediately before and after 6 months’ treatment with nasal CPAP. Results: Nasopharyngeal symptoms were common already before starting nasal CPAP: 74% of patients reported dryness, 53% sneezing, 51% mucus in the throat, 45% blocked nose, and 37% rhinorrhea. During nasal CPAP treatment, severity and frequency of sneezing (75%) and rhinorrhea (57%) increased. This increase was related to the season when nasal CPAP was applied, and was more profound in winter than in summer. Mild abnormalities on rhinoscopy and paranasal sinus X-rays were common both at baseline and at follow-up with no significant change during treatment. Conclusions: Nasopharyngeal problems were found to be frequent in patients with OSAS before nasal CPAP treatment, and tended to increase during the treatment.
Pleural Empyema: An Unusual Presentation of Esophageal Perforation
Authors: Solomonov A. , Best L.A. , Goralnik L. , Rubin A.E. , Yigla M.
Published: April 2003

A 67-year-old patient presented with pleural empyema as the sole manifestation of thoracic esophageal perforation, 2 weeks after accidental fish bone ingestion. Nonspecific chest pain and general deterioration, unusual presenting symptoms in themselves, accounted for the extreme delay in the diagnosis. The empyema was treated surgically, and the esophageal perforation conservatively. Despite the poor prognostic factors, the patient recovered completely after 50 days in hospital.
Massive Pulmonary Hemorrhage due to Cytomegalovirus Infection in a Japanese Patient with Alpha-1-Antitrypsin-Deficient Emphysema
Authors: Tsushima Kenji , Koyama Shigeru , Takematsu Hayato , Okada Kazuyoshi , Hata Satoru , Ichiyoshi Takeo , Seyama Kuniaki , Kubo Keishi
Published: April 2003

Although α1-antitrypsin (AAT) deficiency is one of the most common hereditary diseases and a recognized cause of emphysema in Caucasians, variants of this deficiency are extremely rare among Orientals. We present here a Japanese emphysema patient with the AAT deficiency variant originally identified as Siiyama. After an 8-year follow-up period, the patient suffered from repeated pulmonary Pseudomonas aeruginosa infection for 4 years. He died suddenly of massive pulmonary hemorrhage. The pathologic examination revealed a necrotic hematoma in the right S10 lobe, which exhibited pneumonia due to cytomegalovirus (CMV) infection. Pulmonary hemorrhage due to CMV can occur and be fatal in patients with emphysema and AAT deficiency.
Assessment of Sleep Complaints and Sleep-Disordered Breathing in a Consecutive Series of Obese Patients
Authors: van Kralingen Klaas W. , de Kanter Wanda , de Groot Gerrit H. , Venmans Ben J.W. , van Boxem Ton , van Kerrebroeck Anton R.J. , Postmus Pieter E.
Published: April 2003

Background/Objective: The prevalence of sleep-related complaints (SRC) and the frequency of sleep-disordered breathing (SDB) in obese patients has not been studied extensively. We investigated SRC and SDB in a group of obese persons as part of a preoperative workup for weight reduction (bariatric) surgery. Methods: All consecutive patients attending a weight-loss clinic for evaluation for bariatric surgery were asked to complete a questionnaire. The questionnaire consisted of a section on SRC and a validated general sleep questionnaire (Sleep Wake Experience List). The patients underwent sleep studies in which an Edentrace recorder registered heart rate, chest wall movements by impedance, airflow and oxygen saturation. Results: Fifty-one patients (14 men, 37 women) were evaluated. Mean body mass index (BMI) was 45 kg/m2 (range 33–61). Eighteen patients (35%) demonstrated SDB, defined as (a) an apnea/hypopnea index ≥5, and/or (b) more than 2% of registration time with an oxygen saturation below 90%. There was no difference between these 18 patients and patients who did not exhibit SDB in age, sex, BMI or SRC. Seven patients had SDB of a severity warranting closer investigation and perioperative monitoring. Conclusion: Both SRC and SDB are common in obese patients. Limited nocturnal respiratory monitoring is indicated as part of the preoperative workup for weight reduction surgery.
Immunohistochemical Localization of B7 Costimulating Molecules and Major Histocompatibility Complex Class II Antigen in Pulmonary Sarcoidosis
Authors: Kaneko Yumi , Kuwano Kazuyoshi , Kunitake Ritsuko , Kawasaki Masayuki , Hagimoto Naoki , Miyazaki Hiroyuki , Maeyama Takashige , Tanaka Takuo , Matsuba Tokuji , Hara Nobuyuki
Published: April 2003

Background: Alveolar macrophages (AM) of sarcoidosis have an enhanced capacity to mediate antigen-induced T lymphocyte proliferation. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. Objective: The purpose of this study was to investigate the expression of B7 and MHC molecules in lung tissues from patients with sarcoidosis. Methods: We performed immunohistochemistry for B7-1, B7-2 and MHC class II antigens using transbronchial lung biopsy specimens obtained from patients with sarcoidosis and normal lung parenchyma obtained by lobectomy for solitary pulmonary nodule as controls. Results: B7-1, B7-2 and MHC class II antigen were expressed in epithelioid cells in granulomas in 14 (93.3%), 2 (13.3%) and 9 (60.0%) of 15 patients with sarcoidosis, respectively. These were also expressed in AM in 14 (93.3%), 5 (33.3%) and 12 (80.0%) of 15 patients with sarcoidosis, respectively. The positivitiy of B7-1 was significantly higher than that of B7-2 in both epithelioid cells and AM in sarcoidosis (p < 0.01). Positive signals for B7-1, B7-2 and MHC class II antigen were also found in AM in 9 (90%), 8 (80%) and 8 (80%) of 15 of controls, respectively. However, the intensity of positive signals for B7-1, but not B7-2 or MHC class II antigen in AM was significantly increased in sarcoidosis compared to controls (p < 0.05). Conclusions:  These results suggested that epithelioid cells in granulomas and AM from patients with sarcoidosis had the capability to act as accessory cells and that the accessory function of these cells was shifted to B7-1 rather than B7-2 in sarcoidosis.
Perception of Dyspnea during Histamine- and Methacholine-Induced Bronchoconstriction
Authors: Tetzlaff Kay , Leplow Bernd , ten Thoren Corinna , Dahme Bernd
Published: April 2003

Background: Perception of dyspnea is poorly related to bronchoconstriction and may be influenced by distinct psychophysiologic stimuli. Objective: This study compared the perceived psychophysiologic changes during histamine- and methacholine-induced bronchoconstriction using verbal as well as nonverbal assessment techniques. Methods: Perception of dyspnea was studied during induced bronchoconstriction in 40 atopic subjects randomly ascribed to either histamine (n = 20) or methacholine (n = 20) bronchial challenge. A 100% increase in specific airway resistance (sRaw) indicated airway hyperresponsiveness (AHR). Dyspnea was verbally assessed by the Borg Scale (BS) and the Asthma Symptom Checklist (ASL). A hand dynamometer (HD) served for nonverbal assessment. Both challenge groups did not differ significantly with respect to age, anthropometric data, smoking and lung function before challenge. Results: AHR did not differ between groups but groups differed significantly with respect to the number of symptoms and to symptom intensity reported after challenge. Subjects who underwent the histamine challenge scored significantly higher on both measures derived from the ASL. BS ratings and HD scores correlated significantly but were not significantly related to the degree of AHR. Accurate and poor perceivers could be discriminated by analysis of the relationship between BS and sRaw. Conclusions: These findings suggest that perception of induced dyspnea differs between histamine and methacholine when assessed by a symptom report.
Neutrophil Inflammation and Activation in Bronchiectasis: Comparison with Pneumonia and Idiopathic Pulmonary Fibrosis
Authors: Schaaf Bernhard , Wieghorst Alescha , Aries Sven-Philip , Dalhoff Klaus , Braun Jörg
Published: April 2003

Background: Pulmonary inflammation in bronchiectasis, pneumonia and idiopathic pulmonary fibrosis (IPF) is dominated by neutrophils. Pathophysiologic differences are seen in the degree of airway and tissue destruction. Neutrophil activation and neutrophil proteolytic activity might differ between bronchiectasis, pneumonia and IPF. Objective: The aim of this study was to determine whether levels of inflammatory and protective markers in bronchoalveolar lavage (BAL) differed among cases of bronchiectasis, pneumonia and IPF. Methods: We studied 11 bronchiectasis patients (group 1), 30 pneumonia patients (group 2), 15 IPF patients (group 3) and 12 healthy volunteers (group 4). In the bronchoalveolar lavage fluid, concentrations of α1-proteinase inhibitor, myeloperoxidase (MPO) and elastase-α1PI complex were determined using immunoluminometric assays. Elastase inhibition capacity (EIC) and elastase activity were determined using a colorimetric assay. Results: No EIC, but free elastase activity, was found in 82% of group 1, 20% of group 2, 20% of group 3 and 0% of group 4. Median MPO concentration was highest in group 1: 7,951 ng/ml (16th–84th percentile [16–84%]: 256–36,342) vs. 692 ng/ml (106–2,279; group 2), 332 ng/ml (98–1,657; group 3), and 0.12 ng/ml (0.08–0.26; group 4). Bronchiectasis patients with bronchial Pseudomonas infection showed higher amounts of neutrophils (p < 0.01) and higher elastase activity (p < 0.05) than patients with sterile lavage. Conclusion: Bronchiectasis patients show a severe imbalance between neutrophil activity and protective molecules leading to possible lung destruction. Chronic Pseudomonas infection might trigger neutrophil activation. Future research and treatment strategies should focus on increased bacterial clearance and inhibition of neutrophil toxicity.
Myasthenic Inspiratory Vocal Cord Dysfunction: Efficacy of Nasal Continuous Positive Airway Pressure Treatment
Authors: Todisco Tommaso , Baglioni Stefano , Eslami Amir , Todisco Cristina , Dottorini Maurizio
Published: April 2003

Myasthenic vocal cord dysfunction (VCD), presenting with severe inspiratory stridor, was successfully treated with nasal continuous positive airway pressure (nCPAP), thus giving the medical staff time to make the diagnosis and avoiding intubation or tracheostomy. An important sign leading to diagnosis was the very high MEF50/MIF50 ratio calculated from the flow-volume loop. nCPAP treatment induced prompt remission of stridor and a sharp reduction in the MEF50/MIF50 ratio from 9.90 to 1.36. A review of the literature has shown that VCD with inspiratory stridor is an unusual onset symptom of myasthenia gravis and that nCPAP treatment may avoid emergency oral/tracheal intubation and tracheostomy. After diagnosis, the patient underwent thymectomy, and today, 3 years later, he is well without any further therapy.
A Comparison of Induced and Expectorated Sputum for the Microbiological Diagnosis of Community Acquired Pneumonia
Authors: Bandyopadhyay T. , Gerardi D.A. , Metersky M.L.
Published: April 2003

Background: Sputum induction has proved useful in the diagnosis of Pneumocystis carinii pneumonia and mycobacterial infections but there are scant data on its use in the diagnosis of community-acquired pneumonia (CAP). Objective: To better define the usage of sputum induction by hypertonic saline in the setting of CAP. Methods: A retrospective review of records of patients admitted to a community teaching hospital in the year 1995 with a diagnosis of CAP. Results: Of 492 patients admitted with CAP, 71 (14%) had attempted sputum induction. A group of 66 patients with CAP and attempted sputum collection by spontaneous expectoration was compared with this group. Sputum induction failed to yield a sample in 22 patients (31%). Forty-five of 49 patients (92%) with induced sputum had received prior antibiotics as compared to 23 of 34 patients (68%) with expectorated samples (p < 0.05), due to sputum induction often being attempted later in the hospital course. The diagnostic yield of sputum induction was 14 of 71 (20%) compared to 16 out of 66 (24%) for attempted spontaneously expectorated samples. Antibiotic therapy was changed for 5 of 34 patients (15%) who spontaneously expectorated samples and for 9 of 49 patients (18%) with successful induction. Conclusions: Sputum induction is effective in obtaining sputum in some patients with CAP who fail to expectorate a sample. Attempting induction early, preferably before starting antibiotics, may increase its diagnostic yield.
Difference in the Effects of Low Temperatures on the Tension of Human Pulmonary Artery and Vein Ring Segments
Authors: Suzuki Satoshi , Sugita Makoto , Ono Sadafumi , Song Chun , Kondo Takashi , Fujimura Shigefumi
Published: April 2003

Background: Although limited data suggest that pulmonary flushing with organ preservation solutions should not be performed at too low temperatures, the influence of temperature on pulmonary vascular tone is unclear. Objective: The purpose of this study was to examine the effect of low temperatures of the tension of human pulmonary artery and vein ring segments and the vascular resistance of perfused rat lungs. Methods: 5 sets of human pulmonary artery and vein ring segments were suspended from a force displacement transducer at 37, 24 and 8°C, and the effect of 30 mM K+ on the tension was monitored. The effect of 30 mM K+ on vascular resistance was also examined at low temperatures in 5 perfused rat lungs. Results: Pulmonary artery segments dilated at 24°C, and more significant vasodilatation was observed at 8°C. In contrast, there was a significant constriction of pulmonary veins at 8°C. Vasoconstriction induced by 30 mM K+ at 37°C was significantly inhibited at low temperatures in both pulmonary arteries and veins. In rat lungs, perfusion at 8°C caused a significant increase in pulmonary vascular resistance, even though no further increase was observed in the presence of 30 mM K+. Conclusions: Our data indicate that pulmonary arteries dilate and the veins constrict at 8°C and may increase pulmonary vascular resistance. We conclude that the different effect of low temperatures between pulmonary arteries and veins may explain why pulmonary vascular flushing with organ preservation solutions at room temperature is more satisfactory.
Diffuse Alveolar Hemorrhage following Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Yigla Mordechai , Sprecher Eli , Azzam Zaher , Guralnik Luda , Kapeliovich Michael , Krivoy Norberto
Published: April 2003

We describe a 66-year-old patient with hemoptysis, a drop in hematocrit, hypoxemia and new bilateral alveolar infiltrates after receiving streptokinase for acute myocardial infarction. Markedly increased carbon monoxide diffusion capacity suggested a diagnosis of alveolar hemorrhage. Underlying conditions included congestive heart failure. The patient recovered uneventfully within 7 days of conservative treatment. Alveolar hemorrhage is a rare and often unrecognized life-threatening complication of thrombolytic therapy. Particular attention should be paid to the pulmonary status of patients with congestive heart failure scheduled to receive thrombolytic therapy.
LINAC Radiosurgery for Cavernous Sinus Meningiomas
Authors: Chang, Steven D. , Adler Jr. John R. , Martin David P.
Published: April 2003

Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors. Since 1989, 24 patients with cavernous sinus meningiomas have been treated at Stanford University Medical Center with linear accelerator (LINAC) radiosurgery. The mean age of the patients was 47.8 years (range 28–78). The mean volume treated was 6.83 cm3 (range 0.45–22.45 cm3), covered with an average of 2.3 isocenters (range 1–5).Radiation dose averaged 17.7 Gy (range 14–20 Gy). This group of patients was retrospectively studied by sending clinical questionnaires to both the patient/family and referring physicians, and reviewing clinic charts. In addition, follow-up imaging studies were obtained to measure residual tumor volume. Follow-up averaged 45.6 months (range 19–80). Tumor control (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on MRI imaging 1–3 years after radiosurgery. Neurologic status was improved in 10 patients (42%) and unchanged in 12 patients (50%). There was 1 case of symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All other complications were transient, including 4 cases of trigeminal hypesthesia and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was 100%. Although follow-up is still short, this experience corroborates prior reports that radiosurgery can be used to treat selected small cavernous sinus meningiomas with good to excellent clinical results and minimal morbidity.
Stereotactic Cyst Wall Disruption and Aspiration of Colloid Cysts of the Third Ventricle
Authors: Kumar Krishna , Kelly Michael , Toth Cory
Published: April 2003

Background: Current strategies of surgical therapy for colloid cysts have been associated with low rates of initial success and high rates of morbidity, mortality and recurrence of cysts. Cyst recurrence following simple stereotactic aspiration has been hypothesized to be due to regrowth of the epithelium composing the cyst wall. Methods: We propose a procedure involving stereotactic disruption of the colloid cyst wall with the removal of a portion of the cyst wall followed by aspiration of cyst contents as a surgical therapy for colloid cysts. Results: This procedure was performed in 2 female and 3 male patients who were followed for an average of 49 months with all patients demonstrating immediate improvement of symptoms and resolution of the cyst verified with repeat computerized tomography (CT) scans. There was one incidence of recurrence in an asymptomatic patient at 75 months postoperatively. Conclusion: We propose that stereotactic partial cyst wall disruption and content aspiration may limit recurrence of colloid cysts, thus offering an advantage over simple stereotactic aspiration alone.
Accuracy of Magnetic Resonance Imaging Stereotactic Coordinates with the Cosman-Roberts-Wells Frame
Authors: Carter David A. , Parsai E. Ishmael , Ayyangar Komanduri M.
Published: April 2003

Quality assessment on the accuracy of a Cosman-Roberts-Wells (CRW) magnetic resonance imaging (MRI) stereotactic ring which had nonferrous stainless steel screws and positioning posts and a localizer with petroleum jelly in the fiducials, purchased in 1994, revealed errors of greater than 4 mm with targets in phantoms. Image fusion of objects within the phantom indicated the central area was accurately depicted by CT or MRI. We then tested a newer CRW- MRI ring (MRIA-IHR with titanium screws and posts) and localizer (MRIA-2-LF with fiducials filled with copper sulfate) and found that the MRI stereotactically calculated target coordinates matched both the known position of these targets in the phantom as well as the CT stereotactically calculated coordinates within approximately 1 mm. We also describe excellent superimposition of CT and MRI stereotactically determined surfaces in a recent clinical case using the new hardware. This shows that recent modifications to the CRW-MRI stereotactic system can make it accurate for small targets, but we emphasize that all systems need to undergo ongoing local quality assessment to ensure acceptable accuracy in practice.
Stereotaxy, Navigation and the Temporal Concatenation
Authors: Apuzzo Michael L.J. , Chen Joseph C.T.
Published: April 2003

Nautical and cerebral navigation share similar elements of functional need and similar developmental pathways. The need for orientation necessitates the development of appropriate concepts, and such concepts are dependent on technology for practical realization. Occasionally, a concept precedes technology in time and requires periods of delay for appropriate development. A temporal concatenation exists where time allows the additive as need, concept and technology ultimately provide an endpoint of elegant solution. Nautical navigation has proceeded through periods of dead reckoning and celestial navigation to satellite orientation with associated refinements of instrumentation and charts for guidance. Cerebral navigation has progressed from craniometric orientation and burr hole mounted guidance systems to simple rectolinear and arc-centered devices based on radiographs to guidance by complex anatomical and functional maps provided as an amalgam of modern imaging modes. These maps are now augmented by complex frame and frameless systems which allow not only precise orientation, but also point and volumetric action. These complex technical modalities required and developed in part from elements of maritime navigation that have been translated to cerebral navigation in a temporal concatenation.
Frameless Stereotactic Neurosurgery: Two Steps towards the Holy Grail of Surgical Navigation
Authors: Eljamel M.S.
Published: April 2003

The holy grail of surgical navigation is to provide precise continuous feedback during surgery about the target and its surrounding structures. The first step was the ability of hardware and software technology to allow patient-to-image registration using a multi-potentiometer position-sensing articulated arm system. We used such a system (OAS; Radionics, Burlington, Mass., USA) in 169 consecutive patients with common intracranial lesions. We achieved a mean application accuracy of 2.5 mm, which was sufficiently reliable for most neurosurgical procedures. However, to get the feedback information, the surgeon has to look away from the operative field to the workstation monitor. As psychological studies of manual workers including surgeons indicated that performance is better when the worker is looking in a downward gaze at his hands, the natural progression was to project feedback information between the eyes and the hands. Therefore, the second step was to link tracking technology to the surgical microscope with head-up display. We used such a system (SMN-Zeiss, Germany) in 65 consecutive patients with a mean application accuracy of 1.4 mm. This was again sufficiently reliable for neuronavigation. The head-up display provided continuous feedback to the surgeon about the target, risk zones and areas of interest without the need to interrupt the procedure to get such information. Furthermore, the use of the focal length of SMN with autofocus to perform the registration improved the application accuracy of this technology. The ability of the software to process all MRI sequences (T1, T2, MPR and CISS) allowed us to use a variety of image sequences to delineate the lesion more exquisitely.
Placement of Deep Brain Stimulators into the Subthalamic Nucleus
Authors: Yoon Michael S. , Munz Michael
Published: April 2003

We present our technique for deep brain stimulation (DBS) of the subthalamic nucleus (STN) and include information which may be helpful in general DBS. With the patient in a stereotactic head frame, the anterior and posterior commissures are identified on SPGR-sequence magnetic resonance imaging (MRI). STN coordinates are based on a stereotactic brain atlas at 12 mm lateral, 2 mm posterior and 5 mm caudal to the midcommissural point. Surgical navigation software allows for planning of the trajectory. Electromyography is used to quantitatively measure tremor responses to macrostimulation. Permanent lead placement is confirmed with intraoperative fluoroscopy and postoperative MRI.
Correlation between MRI-Based Stereotactic Thalamic Deep Brain Stimulation Electrode Placement, Macroelectrode Stimulation and Clinical Response to Tremor Control
Authors: Mobin Fardad , De Salles Antonio A.F. , Behnke Eric J. , Frysinger Robert
Published: April 2003

In this study we compared the position of the electronically active contact of the thalamic (Vim) deep brain stimulation (DBS) electrode to the stereotactic location of its tip. Fifteen patients with either Parkinson’s disease (PD) or essential tremor (ET) underwent stereotactic, MRI-based placement of the Medtronic quadripolar DBS electrode. An overall improvement of 69% was achieved in the tremor scores during a period of 1–13 months after implantation of the DBS electrode. Eleven patients with ET showed 70% clinical improvement of tremor, compared to a 58% response observed in the 4 patients with PD. The electrode tip center was 11.2 ± 1.54 mm lateral to the third ventricular wall, 5.38 ± 1.02 mm anterior to the posterior commissure and 2.9 ± 3.57 mm inferior to the level of AC–PC line. The most significant deviation from the planned stereotactic target was observed in the Z-coordinate. In our group of patients, stimulation settings favored the contacts closer to the AC–PC line, correcting the electrode tip position to 0.80 ± 2.84 mm (p < 0.001) inferior to the level of the AC–PC line. In our experience, thalamic DBS offers a reversible and adjustable ‘lesion’ to compensate for the anatomic variabilities encountered in the positioning of the DBS electrode tip.
Vocal Tremor Reduction withDeep Brain Stimulation
Authors: Yoon Michael S. , Munz Michael , Sataloff Robert T. , Spiegel Joseph R. , Heuer Reinhardt J.
Published: April 2003

We present a case illustration of the significant effect that deep brain stimulation (DBS) of the thalamus can have on vocal tremor. A 72-year-old female with a history of essential tremor was noted preoperatively to have a moderate vocal tremor (3 on a scale of 1–5). Following bilateral DBS of the thalamus, the vocal tremor rating improved to 1. Acoustic analysis demonstrated her vocal tremor to be affecting the amplitude of her voice at 5.58 Hz preoperatively, at 1.93 Hz postoperatively with both leads on and at 1.54 Hz with only the left lead on. A videotaped endoscopic view of the patient’s vocal cords (presented at the 1999 ASSFN meeting) clearly illustrated the dramatic changes apparent in the vocal tremor when the stimulators were turned on and off.
Coregistered Ultrasound as a Neurosurgical Guide
Authors: Pallatroni H. , Hartov A. , McInerney J. , Platenik L.A. , Miga M.I. , Kennedy F.E. , Paulsen K.D. , Roberts D.W.
Published: April 2003

Introduction: The dynamic nature and three dimensionality of ultrasound data can be utilized to enhance the capabilities of image guidance systems. Methods: Coregistration of ultrasound data was done using an electromagnetic digitizer, and subsequent ultrasound images were correlated with preoperative MRI studies. Thirty-two patients undergoing craniotomy were investigated in this manner. Results: Phantom testing done with a rigid stylus and 3D ultrasound tracker demonstrated an accuracy of 1.36 ± 1.67 mm in determining the location of a point. Thirty-two clinical cases were coregistered without difficulty. Conclusion: Coregistered ultrasound is a useful methodology that can aid in neuronavigation.
Validation of Freeze-Drying to Visualize Percutaneous 3H-Estradiol Transport: The Influence of Skin Hydration on the Efficacy of the Method
Authors: Neelissen Jan A.M. , Arth Christoph , Schrijvers Ad H.G.J. , Junginger Hans E. , Boddé Harry E.
Published: April 2003

A study was made of the validity of freeze-drying to visualize the distribution of 3H-estradiol in human stratum corneum after topical application of a dry dose, a patch or a buffer solution. Each of these donor formulations was applied to human dermatomed skin for 24 h using Franz permeation cells. Subsequently, small pieces of skin were subjected to cryofixation, freeze-drying, osmium tetroxide vapor fixation, Spurr resin embedding and electron microscopic autoradiography. Stratum corneum from dry dose and patch application experiments was well preserved by freeze-drying, allowing an accurate localization of 3H-estradiol. In contrast, stratum corneum from buffer solution experiments suffered from cryofixation artifacts due to excessive hydration of the skin. The corresponding autoradiographs showed strong redistribution of 3H-estradiol. Thus, the visualization method under investigation has its limitations regarding the hydration level of the skin.
In vivo Noninvasive Evaluation of Hairless Rat Skin after High-Voltage Pulse Exposure
Authors: Vanbever Rita , Fouchard Delphine , Jadoul Anne , De Morre Nathalie , Préat Véronique , Marty Jean-Paul
Published: April 2003

Short high-voltage pulses have recently been shown to dramatically increase and expedite transdermal drug transport via a mechanism hypothesized to involve electroporation. This study addresses tolerance issues of the method in vivo in hairless rat. Chromametry, transepidermal water loss (TEWL), laser Doppler flowmetry (LDF) and corneometry were jointly used for noninvasive sensing of skin biophysical parameters. Slight increases in skin redness, TEWL and LDF values followed the application of electric pulses. The changes in skin capacitance were nonsignificant. The magnitude of the alterations depended on the electrical features of the pulses. When compared to iontophoresis, high-voltage pulses did not induce stronger alterations of skin functions. This report provides the first in vivo demonstration of the safety of the high-voltage pulses proposed for transdermal delivery.
Effects of Systemic Treatment with Liarozole on Cutaneous Inflammation, Epidermal Proliferation and Differentiation in Extensive Plaque Psoriasis
Authors: van Pelt J.P.A. , de Jong E.M.G.J. , de Bakker E.S.M. , van de Kerkhof P.C.M.
Published: April 2003

Liarozole is a novel inhibitor of the enzyme cytochrome P450 which has inhibitory effects on the 4-hydroxylation of retinoic acid. Previous studies have shown that liarozole is effective in the treatment of psoriasis. We performed an immunohistochemical study on the lesional skin from 7 patients with extensive plaque psoriasis, who were treated with systemic liarozole 75 mg BID for a period of at least 2 months. The effects of liarozole treatment on clinical and histological parameters were investigated. In particular, the effect of liarozole on the integrin markers CD11b and CD18 was studied.For immunohistochemistry, three consecutive biopsies were taken: before treatment, after 4, and after 8 weeks of treatment. Clinical scores and side effects were recorded before and during treatment.The medication was well tolerated and only mild side effects were reported, which were comparable with hypervitaminosis A. After 2 months of treatment a statistically significant decrease of the extent of body involvement was observed. In the psoriatic plaque, markers for epidermal proliferation and cutaneous inflammation decreased, and markers for epidermal differentiation increased to values comparable to normal skin. The first therapeutic effects in the psoriatic plaque occurred after 4 weeks of treatment, and consisted of a decreased induration, accompanied by a decrease of the total number of inflammatory infiltrate cells and a decreased epidermal ICAM-1 expression. Already after 4 weeks of treatment, a decrease of CD11b-positive cells was observed. Subsequently, after 8 weeks of treatment the recruitment of cycling epidermal cells and the number of involucrin-positive cell layers decreased.The present study demonstrates that liarozole treatment of psoriasis results in a reduction of aspects of cutaneous inflammation and subsequently a reduction of epidermal proliferation and promotion of differentiation. After 4 weeks of treatment, effects are observed on the epidermal ICAM-1 expression and on the CD11b-positive cell population.
Relevance of Hairless Mouse as an Experimental Model of Percutaneous Penetration in Man
Authors: Simon Gad A. , Maibach Howard I.
Published: April 2003

Since their first description in 1850, hairless mice have been widely used in scientific research. One major aspect of their use is skin pharmacology in general and skin penetration studies in particular. The term ‘hairless mouse’ does not distinguish a unique animal: it is a collective, descriptive name for a large group of different strains of various genetic origin. It is therefore important to precisely define the strain of mice used in a study. The available information on comparative penetration studies in man and in hairless mouse is sometimes contradictory. Some compounds will penetrate in an almost similar manner, whereas others differ in at least one logarithmic order, the human skin being the less permeable. Skin permeability is influenced, among others, by the physicochemical qualities of the compound under investigation. To obtain a clearer view on the suitability of the hairless mouse model in skin penetration studies, it should be useful to study this issue prospectively in a systematic fashion.
Silver Nitrate: Antimicrobial Activity Related to Cytotoxicity in Cultured Human Fibroblasts
Authors: Hidalgo Eduard , Bartolomé Rosa , Barroso Concepción , Moreno Antonio , Domínguez Carmen
Published: April 2003

The aims of this study were to ascertain whether silver nitrate (AgNO3) concentrations below those used in clinical practice inhibit bacterial growth, and in parallel study the cytotoxic effects on human fibroblasts. The cytoprotective effects of fetal calf serum (FCS) were also evaluated. The cytotoxic effects of eight different silver nitrate concentrations were determined by assessing mitochondrial activity of viable cells capable of cleaving tetrazolium salts. Antimicrobial activity of AgNO3, range: 7–550 × 10–5%, was tested against Staphylococcus aureus, Citrobacter freundii, and Pseudomonas aeruginosa. Silver nitrate concentrations exerting antimicrobial effects were: S. aureus, >70 × 10–5%; P. aeruginosa, ≥270 × 10–5%, and C. freundii, ≥550 × 10–5%. With 2% FCS, the lowest AgNO3 concentration studied (7 × 10–5%) showed cytotoxic effects (cell survival 71 ± 19%) at only 2 h of incubation. Under these conditions AgNO3 cytotoxicity was time- and concentration-dependent in all exposure periods. Cytotoxicity was greatly enhanced causing 76% fibroblast growth inhibition at concenctrations of 14 × 10–5% and contact time of 2 h. The AgNO3 concentration of 7 × 10–5% was also cytotoxic with 5% FCS in the media compared with controls, although cell survival was higher than with 2% FCS. The cytoprotective action of FCS was clearly shown at the concentration of 10% at which AgNO3 cytotoxicity of 7 × 10–5% to 28 × 10–5% was partially or completely inhibited. Our results show that AgNO3 at concentrations 100–700 times more diluted than that normally used in clinical practice retained effective inhibitory activity against some of the above-mentioned microorganisms. However, even these concentrations are cytotoxic for cultured fibroblasts. Thus, silver nitrate concentrations up to 100 times more diluted can be used, since they possess bacterial growth-inhibiting power, are less cytotoxic and therefore favour wound healing.