ABSTRACT
PURPOSE: Electrical stimulation of the whole hypoglossal nerve (HGp-ES) has been demonstrated to enlarge the pharynx and improve pharyngeal stability and patency to airflow in all animals studied, but not in humans. The present study was undertaken to better understand the effect of HGp-ES on the human pharynx. METHODS: Eight patients with obstructive sleep apnea who had implanted stimulators with electrodes positioned proximally on the main truck of the hypoglossus were studied under propofol sedation. Pharyngoscopy and air flow measurements at multiple levels of continuous positive airway pressure (CPAP) were performed before and during Hgp-ES. RESULTS: HGp-ES that activates both tongue protrusors and retractors narrowed the pharyngeal lumen at the site of collapse (velopharynx in all subjects) from 1.38 ± 0.79 to 0.75 ± 0.44 cm2, p < 0.05 (measured at mid-range of CPAP levels) and lowered airflow (from 8.88 ± 2.08 to 6.69 ± 3.51 l/min, p < 0.05). Changes in critical pressure (Pcrit) and velopharyngeal compliance were not significant, but oropharyngeal compliance decreased (from 0.43 ± 0.18 to 0.32 ± 0.13 cm2/cmH2O, p < 0.05). No correlation was found between the pattern of change in luminal shape (determined as the ratio of a-p vs. lateral diameter when lowering CPAP) or changes in cross-sectional area and airflow during Hgp-ES. CONCLUSIONS: Our findings indicate that human retractors dominate when stimulated together with the protrusors during HGp-ES. While co-activation of retractors may be beneficial, it should be limited. We speculate that exercises that augment protrusor force may improve the response to hypoglossal stimulation. The exclusion of patients with concentric pharyngeal obstruction should be re-evaluated.
Subject(s)
Electric Stimulation , Hypoglossal Nerve/physiopathology , Sleep Apnea, Obstructive/physiopathology , Adult , Continuous Positive Airway Pressure , Humans , Male , Middle AgedABSTRACT
Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm(2)/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS.
Subject(s)
Airway Resistance/physiology , Electric Stimulation/methods , Hypoglossal Nerve/physiology , Muscle Contraction/physiology , Pharyngeal Muscles/physiology , Pharynx/physiology , Respiration, Artificial/methods , Animals , Male , Muscle Strength/physiology , Pharyngeal Muscles/innervation , Respiratory System Agents , SwineABSTRACT
OBJECTIVE: Structured Clinical Examinations (OSCE) are resource intensive, not practical as teaching tools, and their reliability depends on evaluators. Computer-based case simulations ("virtual patients", VP) have been advocated as useful and reliable tools for teaching clinical skills and evaluating competence. We have developed an internet-based VP system designed both for practice and assessment of medical students. The system uses interactive dialogue with natural language processing, and is designed for history taking, evaluation of physical examination, including recognition of visual findings and heart and lung sounds, and ordering lab-and imaging tests. The system includes a practice modality that provides feedback, and a computerized OSCE. The reliability of our system was assessed over the last three years by comparing the clinical competence of medical students in similar VP and human OSCE. A total of 262 students were evaluated with both exam modalities. The correlation between the two exams scores was highly significant (p<0.001). Alpha Cronbach for the computerized exam was 0.82-0.89 in the 3 years, and was substantially higher than that of the conventional OSCE each year. We conclude that a computerized VP OSCE is a reliable examination tool, with the advantage of providing also a training modality.
Subject(s)
Education, Distance/methods , Education, Medical/methods , Patient Simulation , Physical Examination/methods , Clinical Competence/standards , Computer Simulation , Heart Sounds , Humans , Internet , Language , Medical History Taking , Reproducibility of Results , Respiratory Sounds , Software , Students, MedicalABSTRACT
Chronic stimulation of the hypoglossus nerve may provide a new treatment modality for obstructive sleep apnoea (OSA). In previous studies we observed large differences in response to stimulation of the genioglossus (GG). We hypothesised that both individual patient characteristics and the area of the GG stimulated are responsible for these differences. In the present study, we compared the response to GG electrical stimulation at the anterior area (GGa-ES), which activates the whole GG and the posterior area (GGp-ES), which activates preferentially the longitudinal fibres. Studies were performed in 14 propofol-sedated OSA patients. The parameters evaluated included cephalometry, pressure-flow relationship and pharyngeal shape and compliance assessed by pharyngoscopy. Compared with GGa-ES, GGp-ES resulted in significantly larger decreases in the critical value of end-expiratory pressure (P(crit)) (from 3.8 ± 2.2 to 2.9 ± 3.3 and -2.0 ± 3.9 cmH(2)O, respectively (p<0.001)). Both tongue size and velopharyngeal shape (anteroposterior to lateral ratio) correlated significantly with the decrease in P(crit) during GGp-ES (R = 0.53 and -0.66, respectively; p<0.05). In the patients with the larger tongue size (n = 7), the decrease in P(crit) reached 8.0 ± 2.2 cmH(2)O during GGp-ES. We conclude that directing stimulation to longitudinal fibres of the GG improves the flow-mechanical effect. In addition, patients with large tongues and narrow pharynx tend to respond better to GGp-ES.
Subject(s)
Electric Stimulation Therapy/methods , Pharynx/physiopathology , Sleep Apnea, Obstructive/therapy , Adult , Aged , Continuous Positive Airway Pressure , Humans , Hypnotics and Sedatives/therapeutic use , Male , Middle Aged , Organ Size , Pharynx/innervation , Propofol/therapeutic use , Sleep Apnea, Obstructive/physiopathology , Tongue/anatomy & histology , Tongue/physiopathologyABSTRACT
The present study measured hypotonic pharyngeal collapsibility in subjects not known to have obstructive sleep apnoea (OSA), and assessed the variables that affect collapsibility and the relationship with OSA. The critical value of positive end-expiratory pressure (P(crit)) was measured under the hypotonic condition of anaesthesia in 227 subjects who underwent elective surgery. The risk of OSA in this population was estimated using the Berlin questionnaire. The mean P(crit) for all subjects was positive (above atmospheric), ranging from 0.69 (95% confidence interval (CI) -7.39-8.77) to 4.0 (CI -4.82-12.82) cmH(2)O for subjects with low and high prevalence of OSA, respectively. P(crit) < or = -5 cmH(2)O was only found in 3.1% of the study subjects. In the general population, P(crit) was similar in males and females and correlated positively with increasing age, while a correlation with neck circumference was found only in males. P(crit )accounted for only 12.25% of the variability in OSA risk score. In conclusion, subjects with high critical value of positive end-expiratory pressure are at an increased risk for developing obstructive sleep apnoea. However, the human pharynx is prone to collapse and occludes in most people in the absence of neuromuscular support. Therefore, in most subjects, the level of neuromuscular activity may ultimately determine the occurrence of sleep apnoea.
Subject(s)
Pharynx/physiopathology , Sleep Apnea, Obstructive/diagnosis , Adult , Age Factors , Anesthesia , Anthropometry , Female , Halothane/pharmacology , Humans , Male , Middle Aged , Pharynx/anatomy & histology , Pressure , Prevalence , Propofol/pharmacology , Sleep Apnea, Obstructive/physiopathology , Surveys and QuestionnairesABSTRACT
INTRODUCTION: The role of granulocyte transfusions (GT) in patients with neutropenia-related infections remains controversial. MATERIALS AND METHODS: A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life-threatening infections between 1999 and 2004, is presented. RESULTS: The only grade III-IV toxicity observed in GT recipients was respiratory deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per microl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion. CONCLUSION: GTs are safe and should be considered for patients with life-threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.
Subject(s)
Bacterial Infections/therapy , Blood Transfusion/methods , Granulocytes , Leukocyte Transfusion/methods , Mycoses/therapy , Neutropenia/therapy , Adolescent , Adult , Aged , Bacterial Infections/complications , Blood Donors , Female , Humans , Leukapheresis/methods , Leukocyte Transfusion/adverse effects , Male , Middle Aged , Mycoses/complications , Retrospective Studies , Survival AnalysisABSTRACT
The purpose of the present study was to quantify the mechanical effect of genioglossus stimulation on flow mechanics and pharyngeal cross-sectional area in patients with obstructive sleep apnoea, and to identify variables that determine the magnitude of the respiratory effect of tongue protrusion. The pressure/flow and pressure/cross-sectional area relationships of the velo- and oropharynx were assessed in spontaneously breathing propofol-anaesthetised subjects before and during genioglossus stimulation. Genioglossus contraction decreased the critical pressure significantly from 1.2+/-3.3 to -0.7+/-3.8 cmH(2)O, with individual decreases ranging -0.6-5.9 cmH(2)O. Pharyngeal compliance was not affected by genioglossus contraction. The pharyngeal response to genioglossus stimulation was related to the magnitude of advancement of the posterior side of the tongue, but not to the severity of sleep apnoea, critical pressure, compliance or the shape and other characteristics of the velopharynx. Genioglossus contraction enlarges both the velo- and the oropharynx and lowers the critical pressure without affecting pharyngeal stiffness. The response to genioglossus stimulation depends upon the magnitude of tongue protrusion achieved rather than on inherent characteristics of the patient and their airway.
Subject(s)
Hypoglossal Nerve/physiology , Pharynx/metabolism , Sleep Apnea, Obstructive/metabolism , Sleep Apnea, Obstructive/physiopathology , Adult , Electric Stimulation Therapy , Electroencephalography/methods , Electrooculography/methods , Humans , Male , Middle Aged , Models, Anatomic , Muscles/pathology , Oxygen/metabolism , Pharyngeal Muscles/metabolism , Pharynx/chemistry , Polysomnography/methods , Pressure , Tongue/anatomy & histologyABSTRACT
Positional changes of anatomic structures surrounding the upper airway are known to affect pharyngeal mechanics and collapsibility. We hypothesized that these alterations also affect the ability of the upper airway dilator muscles to enlarge the pharynx by altering their ability to shorten when activated. Using sonomicrometry, we evaluated in seven anesthetized dogs the effects of changes in tracheal and head position on the length of the genioglossus (GG) and the geniohyoid (GH) and the effects of these positional changes on the magnitude of shortening of the two muscles in response to electro- (ES) and chemostimulation (CS). Caudal traction of the trachea lengthened the GG and GH in all dogs, whereas cranial displacement of the trachea and flexion of the head to a vertical position shortened the muscles. Compared with the magnitude of ES-induced shortening in the neutral position, ES-induced shortening of the GG was 144.7 +/- 14.6, 49.3 +/- 4.3, and 33.5 +/- 11.6% during caudal and cranial displacement of the trachea and during head flexion, respectively. Similar effects of the positional changes were found for the GH, as well as for both muscles during respiratory stimulation with P(CO2) of 90 Torr at the end of CO(2) rebreathing, although inspiratory muscle shortening during CS reached only one-quarter to one-third of the magnitude observed during ES. We conclude that positional alterations of anatomic structures in the neck have a dramatic effect on the magnitude of shortening of the activated GG and GH, which may reduce substantially their ability to protect pharyngeal patency.
Subject(s)
Larynx/anatomy & histology , Larynx/physiology , Muscle Contraction/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Pharynx/anatomy & histology , Pharynx/physiology , Adaptation, Physiological/drug effects , Adaptation, Physiological/physiology , Animals , Carbon Dioxide/pharmacology , Dogs , Electric Stimulation , Larynx/drug effects , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , Pharynx/drug effects , Respiratory Mechanics/drug effects , Respiratory Mechanics/physiology , Stimulation, ChemicalABSTRACT
In a previous preliminary study an excess of tumor necrosis factor-alpha (TNF) was found in pleural fluid of patients with complicated parapneumonic effusion (CPPE), and its levels in pleural fluid of these patients were shown to be significantly higher than those in patients with uncomplicated parapneumonic effusion (UCPPE). This larger population study was undertaken to investigate, for the first time, the role of pleural fluid-serum gradient of TNF (TNFgradient) in discrimination between UCPPE and CPPE. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in serum and pleural fluid of 51 patients with UCPPE and 30 patients with nonempyemic CPPE. The mean +/- SEM values of serum TNF (TNFserum), pleural fluid TNF (TNFpf), and TNFgradient in the UCPPE group were 6.65 +/- 0.48 pg/mL, 10.85 +/- 0.74 pg/mL, and 4.2 +/- 0.38 pg/mL respectively, and in the CPPE group they were 7.59 +/- 0.87 pg/mL, 54.02 +/- 5.43 pg/mL, and 46.43 +/- 5.34 pg/mL, respectively. While no significant difference was found between the two groups regarding levels of TNFserum (p = 0.31), a highly significant difference between these two groups was found regarding levels of TNFpf and TNFgradient (p < 0.0001 for both variables). A significant correlation was found between levels of TNFserum and levels of TNFpf in the UCPPE group (r = 0.89, p < 0.0001), but not in the CPPE group (r = 0.18, p < 0.33). TNFgradient at an optimal cut-off level of 9.0 pg/mL was found to be a good marker for discrimination between UCPPE and CPPE (sensitivity, 96.7%, specificity, 98%, accuracy, 97.5%, and p < 0.0001). In conclusion, levels of TNFpf but not TNFserum are significantly higher in CPPEs than those in UCPPEs where TNFgradient at an optimal cut-off level of 9.0 pg/mL is a good marker for discrimination between UCPPE and CPPE.
Subject(s)
Pleural Effusion/diagnosis , Tumor Necrosis Factor-alpha/analysis , Aged , Case-Control Studies , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Pleural Effusion/blood , Pleural Effusion/chemistry , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
OBJECTIVES: This study was undertaken to investigate the correlation, which has not been previously investigated, between levels of tumour necrosis factor-alpha (TNF) and levels of pH, glucose, and lactate dehydrogenase (LDH) in pleural fluid of patients with uncomplicated parapneumonic effusion (UCPPE), and patients with complicated parapneumonic effusion (CPPE). METHODS: Using a commercially-available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 23), and CPPE (n = 15), and were compared with levels of pH, glucose, and LDH in these two groups. RESULTS: The mean +/- SD values of pleural fluid TNF, pH, glucose, and LDH in the UCPPE group were 11.05 +/- 7.65 pg/ml, 7.41 +/- 0.08, 125 +/- 48 mg/dl, and 306 +/- 182 IU/l, respectively. In the CPPE group the values were 56.07 +/- 28.5 pg/ml, 6.82 +/- 0.25, 42 +/- 36 mg/dl, and 2096 +/- 1916 IU/l, respectively. The only significant correlation, which was negative, was found between levels of TNF and pH in the CPPE group (r = -0.62, P = 0.01). Levels of pleural fluid TNF and LDH were significantly higher, and levels of glucose were significantly lower in the CPPE group than in the UCPPE group (P < 0.0001). CONCLUSIONS: This study demonstrates, for the first time that TNF levels correlate inversely with levels of pH in pleural fluid of patients with CPPE but not of patients with UCPPE. This correlation may, in part, explain the pathophysiology of the pleural complications which occur in the presence of CPPE.
Subject(s)
Glucose/metabolism , L-Lactate Dehydrogenase/metabolism , Pleural Effusion/metabolism , Pneumonia, Bacterial/complications , Tumor Necrosis Factor-alpha/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Pleural Effusion/chemistry , Pleural Effusion/etiologyABSTRACT
BACKGROUND: Several studies have shown that serum levels of tumor necrosis factor-alpha (TNF) are significantly elevated in patients with acute and chronic liver diseases, where these elevations are independent of the etiology of the underlying disease. Serum levels of TNF are significantly higher in patients with cirrhosis than in those without cirrhosis, reaching the highest levels in decompensated cirrhosis. It has also been shown that plasma levels of TNF correlate with the severity of hepatic encephalopathy (HE) in fulminant hepatic failure. However, still there are no published data regarding the relationship between blood levels of TNF and the presence or severity of HE in patients with chronic liver failure. AIM: The aim of this study is to determine the relationship between serum levels of TNF and clinical grades of HE in patients with liver cirrhosis. METHODS: Using a commercially available high-sensitivity enzyme-linked immunosorbent assay kit, serum levels of TNF were measured in 74 patients with liver cirrhosis in various clinical grades of HE (grades 0-4). RESULTS: The mean+/-SEM values of serum levels of TNF at presentation in patients with grade 0 of HE (n=23), grade 1 (n=12), grade 2 (n=14), grade 3 (n=16), and grade 4 (n=9) were 4.50+/-0.46, 9.10+/-1.0, 12.98+/-1.22, 21.51+/-2.63, and 58.26+/-19.7 pg/ml, respectively. A significant positive correlation was found between serum levels of TNF and the severity of HE (P<0.0001). CONCLUSION: Serum levels of TNF correlate positively with the severity of HE in patients with chronic liver failure.
Subject(s)
Hepatic Encephalopathy/blood , Severity of Illness Index , Tumor Necrosis Factor-alpha/analysis , Aged , Ascites/etiology , Ascites/pathology , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/pathology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , MaleABSTRACT
High concentrations of tumor necrosis factor-a (TNF), as well as excess of polymorphonuclear leukocytes (PMNs), are present in pleural fluid of patients with complicated parapneumonic effusion (CPPE). Several studies have shown that PMNs are capable of secreting TNF. However, the correlation between levels of TNF and PMN counts in pleural fluid of patients with parapneumonic effusion has not been previously evaluated. This study was undertaken to evaluate this correlation. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 22), and CPPE (n = 14), and were compared with PMN count in pleural fluid of these patients. The mean +/- SD values of pleural fluid TNF and PMN count in the UCPPE group the group were 10.15 +/- 6.48 pg/mL and 3,452 +/- 2,878 cells/mm3, respectively, and in the CPPE group the values were 55.51 +/- 29.49 pg/mL and 25,261 +/- 11,733 cells/mm3, respectively. Levels of pleural fluid TNF and PMN counts in the CPPE group were significantly higher than in the UCPPE group (p <0.0001). A significant correlation was found between levels of pleural fluid TNF and PMN counts in the CPPE group (r = 0.57, p = 0.03) and also in the UCPPE group (r = 0.44, p = 0.04). The results of this study indicate that in pleural fluid of patients with UCPPE or CPPE, levels of TNF correlate positively with PMN counts, and PMNs might be an important source of TNF production in pleural fluid of these patients, particularly in those with CPPE.
Subject(s)
Neutrophils/cytology , Pleural Effusion/immunology , Tumor Necrosis Factor-alpha/metabolism , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Humans , Leukocyte Count , Male , Middle AgedABSTRACT
Omeprazole is a potent proton pump inhibitor and usually is well tolerated. Adverse effects of this drug have been reported in up to 5% of patients, most of which are trivial and disappear rapidly on discontinuation of the drug. Skin adverse reactions attributed to omeprazole are uncommon and include rashes, urticaria, angio-oedema, acute disseminated epidermal necrolysis, lichen spinulosus, and contact dermatitis. Cutaneous leucocytoclastic vasculitis (CLV) has not been previously reported in association with omeprazole. The development of CLV in an elderly patient four weeks after starting treatment with omeprazole is described.
Subject(s)
Anti-Ulcer Agents/adverse effects , Drug Hypersensitivity/etiology , Omeprazole/adverse effects , Vasculitis, Leukocytoclastic, Cutaneous/chemically induced , Aged , Anti-Ulcer Agents/therapeutic use , Drug Hypersensitivity/pathology , Duodenal Ulcer/drug therapy , Female , Humans , Omeprazole/therapeutic use , Vasculitis, Leukocytoclastic, Cutaneous/pathologyABSTRACT
Computerized prescription of drugs is expected to reduce the number of many preventable drug ordering errors. In the present study we evaluated the usefullness of a computerized drug order entry (CDOE) system in reducing prescription errors. A department of internal medicine using a comprehensive CDOE, which included also patient-related drug-laboratory, drug-disease and drug-allergy on-line surveillance was compared to a similar department in which drug orders were handwritten. CDOE reduced prescription errors to 25-35%. The causes of errors remained similar, and most errors, on both departments, were associated with abnormal renal function and electrolyte balance. Residual errors remaining on the CDOE-using department were due to handwriting on the typed order, failure to feed patients' diseases, and system failures. The use of CDOE was associated with a significant reduction in mean hospital stay and in the number of changes performed in the prescription. The findings of this study both quantity the impact of comprehensive CDOE on prescription errors and delineate the causes for remaining errors.
Subject(s)
Drug Prescriptions/standards , Medication Errors/prevention & control , Medication Systems, Hospital , IsraelABSTRACT
Gastrointestinal autonomic nerve (GAN) tumours form a distinct subcategory of gastrointestinal stromal tumours, and are thought to originate from the enteric autonomic plexus. To date, a total of 45 cases have been documented in the literature; a few of these cases were associated with neurofibromatosis type 1 (NF-1). Bowel perforation due to other gastrointestinal stromal tumours has been reported only twice, but never in association with a GAN tumour. We describe a 40-year-old woman with NF-1 who had bowel perforation due to a GAN tumour. The patient underwent radical surgical resection and remained tumour free for at least 4 years, which may indicate a good prognosis.
Subject(s)
Autonomic Nervous System Diseases/complications , Intestinal Perforation/etiology , Neurofibromatosis 1/complications , Peripheral Nervous System Neoplasms/complications , Adult , Autonomic Nervous System Diseases/surgery , Female , Humans , Intestinal Perforation/diagnosis , Intestinal Perforation/surgery , Neurofibromatosis 1/surgery , Peripheral Nervous System Neoplasms/surgery , PrognosisABSTRACT
Obstructive sleep apnea (OSA) is a common disorder of the middle aged and elderly. It results from the decrease in upper airway muscle (UAM) tone that occurs during sleep. It is unclear whether age-related changes in UAM could constitute a contributory mechanism to the increased prevalence of OSA with increasing age, and previous papers evaluating the effects of aging on UAM in rats reported conflicting results. In the present study, we compared, in four age groups of Wistar rats (6-24 months), fiber-type distribution, mean cross-sectional fiber area and succinate dehydrogenase optical density of dilating and non-dilating UAM, and the diaphragm. Succinate dehydrogenase optical density, a marker of oxidative capacity, decreased significantly after the age of 6 months in all muscles (except for the sternohyoid), particularly in the genioglossus, the main tongue protrudor. In this muscle, we also found a significant decrease in type IIa and an increase in IIb fibers after the age of 18 months. Age-related changes in fiber-type distribution in other muscles were mostly insignificant. Dilating UAM could not be distinguished from their non-dilating neighboring muscles by their histochemical properties or aging-related changes. The aging-related changes observed in the present study may decrease UAM endurance, particularly that of the main tongue protrudor, the genioglossus.
Subject(s)
Aging/physiology , Respiratory Muscles/anatomy & histology , Respiratory Muscles/metabolism , Animals , Male , Muscle Fibers, Skeletal/classification , Oxidation-Reduction , Pharyngeal Muscles/anatomy & histology , Pharyngeal Muscles/metabolism , Rats , Rats, Wistar , Succinate Dehydrogenase/metabolism , Tongue/anatomy & histology , Tongue/metabolismABSTRACT
Tetramethylrosamine (TMR) is excluded from P-glycoprotein (MDR1)-enriched cell lines, but it stains efficiently MDR1-poor parent lines. Application of the TMR resistance assay to cells obtained from chronic myelogenous leukaemia (CML) patients revealed, in all individuals, a significant resistance compared with healthy donors (P < 0.001). Cells from the same patients at later phases exhibited a further increase in TMR resistance. Doxorubicin was excluded from all cell samples obtained from CML patients at presentation. The resistance to TMR and doxorubicin was energy-dependent, and was not modulated by inhibitors of MDR1 and multidrug-resistance protein-1 (MRP1). Transcription of mRNAs suspected as relevant to multidrug resistance was assessed using comparative reverse transcription polymerase chain reaction. All cells from the CML patients transcribed high levels of MRP3, MRP4 and MRP5 compared with healthy donors. Low levels of MDR1, MRP1, MRP2, MRP6, lung resistance-related protein and anthracycline resistance-associated protein were equally transcribed in cells from healthy donors and CML patients. These results indicated that neither MDR1 nor MRP1 mediate the resistance in these cells. Our results shed light on a resistance mechanism operative in CML patients, which, together with the resistance to apoptosis, is responsible for the lack of response of CML patients to induction-type protocols used to treat acute myeloid leukaemia patients.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Drug Resistance, Multiple , Genes, MDR , Heterocyclic Compounds, 3-Ring , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Multidrug Resistance-Associated Proteins , Pyruvate Dehydrogenase Complex , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP-Binding Cassette Transporters/genetics , Adult , Case-Control Studies , Dihydrolipoyllysine-Residue Acetyltransferase , Doxorubicin , Fungal Proteins/genetics , Humans , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Rhodamine 123 , Rhodamines , Ribosomal Proteins/genetics , Transcription, GeneticABSTRACT
An elderly patient with paraneoplastic cutaneous leukocytoclastic vasculitis (CLV) leading to the discovery of an as-yet asymptomatic, potentially surgically curable squamous cell carcinoma of the lung is presented. This type of vasculitis has not been previously described in association with this type of lung cancer. Since vasculitic paraneoplastic syndromes, including CLV, may develop before the clinical presentation of malignant tumors, the present case and others previously reported strongly suggest that in apparently idiopathic CLV, patients should be evaluated for the presence of occult malignancy that could be curable by early detection.
Subject(s)
Carcinoma, Squamous Cell/diagnosis , Lung Neoplasms/diagnosis , Paraneoplastic Syndromes , Skin Diseases/etiology , Vasculitis, Leukocytoclastic, Cutaneous/etiology , Aged , Carcinoma, Squamous Cell/complications , Humans , Lung Neoplasms/complications , MaleABSTRACT
Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.
Subject(s)
Sleep Apnea, Obstructive/physiopathology , Sleep/physiology , Tongue/physiology , Wakefulness/physiology , Adult , Electric Stimulation , Humans , Hypopharynx/physiology , Middle Aged , Mouth Floor/physiology , Muscle Tonus/physiology , Polysomnography , Respiratory MechanicsABSTRACT
Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is very rare, and to the best of our knowledge, only five cases of liver injury in association with paroxetine have previously been reported in the medical literature. We describe the clinical, biochemical, and pathological findings in a patient with paroxetine hepatotoxicity, which was reversed after withdrawal of the drug. The present case and the others previously reported suggest that hepatotoxicity should be taken into account as a rare complication, sometimes severe, that may occur with paroxetine.