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2.
ESMO Open ; 7(4): 100527, 2022 08.
Article in English | MEDLINE | ID: mdl-35843080

ABSTRACT

BACKGROUND: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. PATIENTS AND METHODS: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. RESULTS: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. CONCLUSION: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carbazoles , Crizotinib , Humans , Japan , Piperidines , Protein Kinase Inhibitors , Survival Analysis
3.
Anticancer Res ; 38(6): 3567-3571, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29848711

ABSTRACT

BACKGROUND/AIM: Osimertinib has demonstrated promising efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC). We investigated the efficacy of osimertinib in such patients presenting with pleural effusion, which has been unclear to date. PATIENTS AND METHODS: The medical records of all patients treated with osimertinib for advanced NSCLC with EGFR T790M between April 2016 and July 2017 at our Institution were retrospectively reviewed. Time to treatment failure (TTF) and overall survival (OS) were determined as endpoints. RESULTS: Twenty-three patients (seven with pleural effusions) were treated with osimertinib. Patients with pleural effusion had significantly shorter median TTF than those without (3.7 vs. 12.8 months, respectively, p=0.021), as well as shorter median OS (7.8 months vs. not attained, respectively, p=0.002). Metastasis to the brain, bone, and liver did not significantly influence our endpoints. CONCLUSION: Osimertinib monotherapy is less effective in patients with NSCLC with pleural effusions.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Mutation , Piperazines/therapeutic use , Pleural Effusion/complications , Acrylamides , Adult , Aged , Aniline Compounds , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/genetics , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/complications , Lung Neoplasms/genetics , Male , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Treatment Outcome
4.
Anticancer Res ; 38(3): 1783-1788, 2018 03.
Article in English | MEDLINE | ID: mdl-29491117

ABSTRACT

BACKGROUND/AIM: Although afatinib has a strong efficacy, it can be toxic; hence, we aimed to determine markers of response to afatinib in order to assess prognosis. PATIENTS AND METHODS: Information on clinical background, therapeutic effects, and adverse events was collected retrospectively at one Institution from patients treated with afatinib as initial epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). We examined the relationship between different adverse events and their effects on prognosis. RESULTS: Afatinib was used in 32 patients as the initial EGFR-TKI. Adverse events of grade 3 or higher including diarrhoea (12.5%), paronychia (6.3%), and stomatitis (3.1%) were experienced by patients. The median progression-free survival (PFS) was 15.4 months. A relationship between skin rash severity and PFS was observed. CONCLUSION: Grade 2 or higher skin rash might be a marker for long-term efficacy of afatinib when administered as a first-line treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Exanthema/chemically induced , Lung Neoplasms/drug therapy , Quinazolines/adverse effects , Adult , Afatinib , Aged , Aged, 80 and over , Diarrhea/chemically induced , Disease-Free Survival , Female , Humans , Male , Middle Aged , Paronychia/chemically induced , Prognosis , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Retrospective Studies , Stomatitis/chemically induced , Treatment Outcome
5.
Br J Radiol ; 87(1039): 20140051, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24834476

ABSTRACT

OBJECTIVE: To compare the pulmonary thin-section CT findings in patients with seasonal influenza virus pneumonia with Streptococcus pneumoniae pneumonia. METHODS: The study group included 30 patients (20 males and 10 females; age range, 20-91 years; mean age, 55.9 years) with seasonal influenza virus pneumonia and 71 patients (47 males and 24 females; age range, 27-92 years; mean age, 67.5 years) with S. pneumoniae pneumonia. RESULTS: The proportion of community-acquired infection was significantly higher in patients with influenza virus pneumonia than with S. pneumoniae pneumonia (p = 0.001). CT findings of ground-glass attenuation (GGA) (p = 0.012) and crazy-paving appearance (p = 0.03) were significantly more frequent in patients with influenza virus pneumonia than with S. pneumoniae pneumonia. Conversely, consolidation (p < 0.001), mucoid impaction (p < 0.001), centrilobular nodules (p = 0.04) and pleural effusion (p = 0.003) were significantly more frequent in patients with S. pneumoniae pneumonia than in those with influenza virus pneumonia. CONCLUSION: Pulmonary thin-section CT findings, such as consolidation and mucoid impaction may be useful in distinguishing between seasonal influenza virus pneumonia and S. pneumoniae pneumonia. ADVANCES IN KNOWLEDGE: (1) Distinguishing seasonal influenza virus pneumonia with S. pneumoniae pneumonia is important. (2) The CT findings of GGA and crazy-paving appearance were more frequently found in patients with influenza virus pneumonia than in patients with S. pneumoniae pneumonia, whereas consolidation, mucoid impaction, centrilobular nodules and pleural effusion were more frequently found in patients with S. pneumoniae pneumonia.


Subject(s)
Influenza, Human/diagnostic imaging , Pneumonia, Pneumococcal/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Community-Acquired Infections/diagnostic imaging , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Pleural Effusion/diagnostic imaging , Pleural Effusion/etiology , Pneumonia, Pneumococcal/complications , Retrospective Studies , Young Adult
7.
J Clin Pathol ; 61(9): 1062-3, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18552170

ABSTRACT

A case of Legionella pneumophila pneumonia with rhabdomyolysis-induced acute tubulointerstitial nephritis (ATIN) and prolonged renal dysfunction is presented. The patient was a 54-year-old man, admitted with high-grade fever, ataxia and muscle dysfunction; chest roentgenogram showed multilobular infiltrations. L pneumophila was detected in his sputum and urine, by PCR and by culture, and L pneumophila pneumonia was diagnosed. Despite antimicrobial treatment, he developed renal failure and rhabdomyolysis. Renal biopsy showed the presence of myoglobin casts that occluded the distal tubuli and tubulointerstitial nephritis, leading to the diagnosis of rhabdomyolysis-induced ATIN. Renal function subsequently normalised, and he was discharged. This is believed to be the first pathological evidence of involvement of rhabdomyolysis in legionellosis-associated ATIN.


Subject(s)
Kidney/pathology , Legionella pneumophila , Legionnaires' Disease/pathology , Nephritis, Interstitial/pathology , Rhabdomyolysis/pathology , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Ciprofloxacin/therapeutic use , Humans , Legionnaires' Disease/complications , Legionnaires' Disease/drug therapy , Male , Middle Aged , Nephritis, Interstitial/drug therapy , Nephritis, Interstitial/etiology , Rhabdomyolysis/complications , Rhabdomyolysis/drug therapy , Rifampin/therapeutic use
8.
Respiration ; 72(5): 480-5, 2005.
Article in English | MEDLINE | ID: mdl-16210886

ABSTRACT

BACKGROUND: Inhaled steroids are currently the most important drugs for asthma patients, but compliance tends to be low. Compliance could be improved by reducing the number of daily administrations. OBJECTIVES: In the present study, we compared once- and twice-daily administration of fluticasone propionate (FP) to determine the differences in efficacy. METHODS: Subjects were 40 patients diagnosed with bronchial asthma with stable symptoms and pulmonary functions who were on twice-daily FP administration of 100 microg. There were 14 men and 26 women ranging from 29 to 72 years of age. After a 4-week observation period, subjects were randomized into two administration groups by the envelope method and followed for 8 weeks: group A, once-daily administration (200 microg of FP at night), and group B, twice-daily administration (100 microg of FP in the morning and at night). Clinical symptoms, pulmonary functions and airway responsiveness were compared between these two groups. RESULTS: No significant deterioration in clinical symptoms, pulmonary functions and airway responsiveness were observed in group A compared with group B. CONCLUSIONS: These results demonstrate that once-daily FP administration is as effective as twice-daily administration, and that it may improve the compliance for inhaled steroids.


Subject(s)
Androstadienes/administration & dosage , Asthma/drug therapy , Bronchodilator Agents/administration & dosage , Administration, Inhalation , Adult , Bronchial Provocation Tests , Drug Administration Schedule , Female , Fluticasone , Forced Expiratory Volume , Humans , Male , Middle Aged , Treatment Outcome
9.
Aliment Pharmacol Ther ; 21(5): 559-66, 2005 Mar 01.
Article in English | MEDLINE | ID: mdl-15740539

ABSTRACT

BACKGROUND: It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. AIM: To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. METHODS: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication. RESULTS: Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels. CONCLUSIONS: The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate.


Subject(s)
Adenocarcinoma/pathology , Adenoma/pathology , Helicobacter Infections/drug therapy , Helicobacter pylori , Stomach Neoplasms/pathology , Adenocarcinoma/microbiology , Adenoma/microbiology , Aged , Aged, 80 and over , Endoscopy, Gastrointestinal , Female , Follow-Up Studies , Gastrins/metabolism , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Middle Aged , Pepsinogen A/blood , Stomach Neoplasms/blood , Stomach Neoplasms/microbiology
10.
Br J Dermatol ; 151(3): 557-64, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15377340

ABSTRACT

BACKGROUND: Barium sulphate, a stable inorganic material, has been used in contrast media and cosmetic products because of its stability. As a negative external electric potential accelerates the skin barrier repair after barrier disruption, we hypothesized that topical application of barium sulphate may affect the skin barrier recovery rate depending on its zeta potential. OBJECTIVES: To investigate whether barium sulphate particles in aqueous solution have different zeta potentials depending on their surface structure, and to investigate the possible relation between zeta potential and skin barrier recovery rate. METHODS: Mice were subjected to tape stripping to disrupt barrier function, or were treated with acetone and kept in a dry environment to induce epidermal hyperplasia. They were then treated with different forms of barium sulphate, and barrier recovery was monitored by measurements of transepidermal water loss. RESULTS: There was a significant correlation between the barrier recovery rate and zeta potential of barium sulphate applied topically. Barium sulphate with a negative zeta potential significantly accelerated barrier recovery, but barium sulphate with a positive zeta potential did not accelerate or even delayed barrier repair. Barium sulphate with a negative zeta potential had an X-ray diffraction pattern different from that with a positive potential. The distribution of calcium in the epidermis was also influenced by the polarity of zeta potential. CONCLUSIONS: These findings suggest a new pharmacological approach towards altering barrier function or epidermal hyperplasia with inorganic particles in healthy and diseased skin.


Subject(s)
Barium Sulfate/therapeutic use , Epidermis/drug effects , Water Loss, Insensible/drug effects , Administration, Cutaneous , Animals , Barium Sulfate/chemistry , Calcium/metabolism , Electrochemistry , Electrophysiology , Epidermis/metabolism , Epidermis/pathology , Hyperplasia/prevention & control , Mice , Mice, Hairless , Microscopy, Electron, Scanning , Structure-Activity Relationship , Wound Healing/drug effects , X-Ray Diffraction
11.
Eur Respir J ; 22(1): 106-12, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12882459

ABSTRACT

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of <-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment. A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief. The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950. It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of <-950 HU are related to the change in forced expiratory volume in one second and residual volume.


Subject(s)
Asthma/diagnostic imaging , Asthma/physiopathology , Adult , Aged , Analysis of Variance , Asthma/drug therapy , Bronchodilator Agents/administration & dosage , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Spirometry , Statistics, Nonparametric , Tomography, X-Ray Computed
12.
Ann Hematol ; 82(1): 61-3, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12574969

ABSTRACT

A periodic fall of platelet number characterizes an acquired pathological condition named cyclic thrombocytopenia. We describe an unusual case of polycythemia vera in which the episodes of thrombocytopenia were followed regularly by thrombocytosis. The period of platelet count fluctuation was about 50 days, with the counts ranging from 34 to 820 x 10(9)/l. Bone marrow megakaryocytes were decreased in number during platelet nadir. Circulating thrombopoietin levels fluctuated out of phase with the platelet count. We suggest that at least some cases of polycythemia vera may have an unstable hematopoietic stem cell pool in nature, which could contribute to the development of unprovoked cyclic thrombocytopenia.


Subject(s)
Periodicity , Polycythemia Vera/complications , Thrombocytopenia/complications , Aged , Aged, 80 and over , Bone Marrow Cells/pathology , Humans , Male , Megakaryocytes/pathology , Platelet Count , Polycythemia Vera/blood , Polycythemia Vera/pathology , Recurrence , Thrombocytopenia/blood , Thrombocytopenia/pathology , Thrombocytosis/blood , Thrombocytosis/complications , Thrombocytosis/pathology , Thrombopoietin/blood
13.
Ann Hematol ; 81(9): 538-9, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12373358

ABSTRACT

A 16-year-old boy with refractory acute myelogenous leukemia developed Fournier's gangrene as an early complication after two-antigen HLA-mismatched unrelated cord blood stem cell transplantation. On day 25 after the transplantation, he noted abrupt onset of penile swelling with miction pain. The penile inflammation rapidly extended posteriorly to involve the scrotum and perianal tissues, inferiorly to involve the thighs, and superiorly up the lower abdominal region within the next 36 h, and he died from sepsis on day 27. Fournier's gangrene presenting as a genitoperineal necrotizing fasciitis should be considered as a potential complication in umbilical-cord blood recipients in the cytopenic post-transplant phase.


Subject(s)
Cord Blood Stem Cell Transplantation/adverse effects , Fournier Gangrene/etiology , Adolescent , Fasciitis, Necrotizing/etiology , Fatal Outcome , Fournier Gangrene/pathology , Histocompatibility , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Male , Sepsis , Transplantation, Homologous/adverse effects , Transplantation, Homologous/immunology
14.
Ann Hematol ; 81(6): 350-1, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12107569

ABSTRACT

A 67-year-old woman with previously untreated essential thrombocythemia developed bilateral adrenal hemorrhage. She had no known vascular risk factors including smoking, diabetes mellitus, hypertension, and hypercholesterolemia. Her platelet count was 921 x 10(9)/l. She received preemptive steroid therapy to prevent the occurrence of adrenal crisis, but 5 weeks later the replacement therapy was discontinued because the patient fully recovered with a normal adrenocorticotropic hormone stimulation test. Thereafter, she remained well for more than 4 years with a platelet count ranging from 600 to 800 x 10(9)/l. Although adrenal hemorrhage is very rare, it can occur as a hemorrhagic complication of essential thrombocythemia.


Subject(s)
Adrenal Gland Diseases/etiology , Hemorrhage/etiology , Thrombocythemia, Essential/complications , Female , Humans , Middle Aged
15.
J Med Invest ; 48(3-4): 147-56, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11694954

ABSTRACT

Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation and accelerates osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization due to motor paralysis from injury of the central nervous system or peripheral nerves, application of cast to treat fractures, a common causes of disuse osteoporosis. Imaging diagnosis shows coarse trabecular pattern and thinning of cortical bones. Bone metabolism markers have been used to evaluate bone metabolism. From the viewpoint of bone metabolism, antiresorptive agents should be administered to inhibit bone resorption. Rehabilitation, including bed positioning, therapeutic exercise and electrical stimulation, should be prescribed to subject the atrophied bone to an appropriate level of mechanical stress. In spite of these aggressive and continuous treatments, most cases of disuse osteoporosis require a long time for bone to recover its bone mineral density and strength. Hence, we have to keep in mind that there are no treatments better than prophylaxis of disuse osteoporosis.


Subject(s)
Immobilization/adverse effects , Osteoporosis/etiology , Paralysis/complications , Autoimmune Diseases/complications , Bed Rest/adverse effects , Biomarkers , Bone Resorption/etiology , Bone Resorption/metabolism , Bone Resorption/prevention & control , Diagnostic Imaging , Diphosphonates/therapeutic use , Electric Stimulation Therapy , Fractures, Bone/complications , Humans , Osteoarthritis/complications , Osteoblasts/metabolism , Osteoclasts/metabolism , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Osteoporosis/metabolism , Osteoporosis/prevention & control , Osteoporosis/rehabilitation , Physical Therapy Modalities , Radiography , Signal Transduction , Spinal Cord Injuries/complications , Stress, Mechanical , Stroke/complications , Weight-Bearing
16.
Nihon Kokyuki Gakkai Zasshi ; 39(7): 471-5, 2001 Jul.
Article in Japanese | MEDLINE | ID: mdl-11579525

ABSTRACT

In March 1995, a 54-year-old woman was admitted to a hospital because of exertional dyspnea and her condition was diagnosed as primary pulmonary hypertension. In September 1996, respiratory difficulty and hemosputum were woted. The chest computed tomographic scan showed diffuse micronodular opacities, and she was admitted to our hospital for examination of other pulmonary conditions giving rise to pulmonary hypertention. However no lung biopsy could be performed, because the pulmonary arterial pressure was too high. Although the patient received medication, she died of progressive right heart failure. The pathological diagnosis at autopsy was pulmonary capillary hemangiomatosis (PCH). Although PCH is a very rare disease that causes secondary pulmonary hypertension, it is important to distinguish it from primary pulmonary hypertension and pulmonary veno-occlusive disease.


Subject(s)
Hemangioma, Capillary/complications , Hypertension, Pulmonary/etiology , Lung Neoplasms/complications , Diagnosis, Differential , Fatal Outcome , Female , Hemangioma, Capillary/diagnosis , Hemangioma, Capillary/pathology , Humans , Hypertension, Pulmonary/diagnosis , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Middle Aged , Pulmonary Veno-Occlusive Disease
17.
Thorax ; 56(11): 851-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11641509

ABSTRACT

BACKGROUND: Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. METHODS: Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than -950 HU (RA(950)) on high resolution CT (HRCT) scans. RESULTS: In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%TLCO, %TLCO/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. CONCLUSIONS: Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.


Subject(s)
Asthma/diagnostic imaging , Adult , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Asthma/physiopathology , Case-Control Studies , Female , Forced Expiratory Volume/physiology , Functional Residual Capacity/physiology , Humans , Male , Maximal Midexpiratory Flow Rate/physiology , Middle Aged , Plethysmography, Whole Body , Regression Analysis , Residual Volume/physiology , Severity of Illness Index , Statistics, Nonparametric , Tomography, X-Ray Computed/methods , Total Lung Capacity/physiology , Vital Capacity/physiology
18.
Endocr J ; 48(4): 443-52, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11603566

ABSTRACT

There is accumulating evidence that interleukin-1 (IL-1) levels are increased locally at the site of active bone resorption in a variety of diseases including osteoporosis, periodontal disease and rheumatoid arthritis. However, the pathogenic role of IL-1 in bone loss remains to be fully elucidated. We present here additional evidence that IL-1beta enhances endothelial activation and thereby stimulates mobilization of peripheral blood mononuclear cells (PBMCs) from luminal to abluminal spaces across the endothelium. Furthermore, IL-1beta stimulates the differentiation of PBMCs into osteoclast-like cells with bone-resorbing activity in the presence of human osteoblastic SaOS-2 cells without systemic hormones. These findings provide circumstantial evidence for the hypothesis that IL-1beta generated in the bone microenviroment plays a stimulatory role in PBMC mobilization from the peripheral circulation and their subsequent differentiation into osteoclast-like cells in the bone tissue. In addition, the present study supports the notion that osteoclast progenitor cells might be derived from the peripheral circulating blood mononuclear cells in human.


Subject(s)
Cell Differentiation , Endothelium, Vascular/cytology , Interleukin-1/pharmacology , Leukocytes, Mononuclear/cytology , Osteoblasts/physiology , Osteoclasts/cytology , Acid Phosphatase/analysis , Antibodies, Monoclonal , Bone Resorption , Cell Adhesion , Cell Line , Cell Movement , Chemotaxis, Leukocyte , Coculture Techniques , Humans , Isoenzymes/analysis , Osteoclasts/enzymology , Stem Cells/cytology , Tartrate-Resistant Acid Phosphatase , Umbilical Veins
19.
J Appl Physiol (1985) ; 91(5): 2334-41, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11641378

ABSTRACT

We examined the effect of weight bearing (WB) on muscle recovery after nerve injury. Rats were housed in individual cages for 2 wk under WB or hindlimb suspension (HS) after being subjected to sciatic nerve compression for 1 wk. Sham operated on rats served as controls (sham group). We used 31P- and 19F-nuclear magnetic resonance spectroscopy combined with histochemical, physiological, and biochemical techniques to assess the outcome in the three groups. Creatine kinase-BB (CK-BB) mRNA levels expression, CK activity, and type I fiber density in the WB group were elevated compared with those in the HS group. In addition, sciatic functional index, tetanic tension, energy state, and local circulation dynamics of the WB group were greater than those of the HS group. These results suggested that WB plays an important role in muscle regeneration, inhibits the reduction of CK activity, and facilitates the activation of neural recovery, energy state, and local circulation dynamics.


Subject(s)
Motor Neurons/physiology , Muscle, Skeletal/injuries , Sciatic Nerve/injuries , Weight-Bearing/physiology , Adenosine Triphosphatases/metabolism , Animals , Creatine Kinase/metabolism , Creatine Kinase, BB Form , Electric Stimulation , Energy Metabolism/physiology , Hindlimb/innervation , Hindlimb/physiology , Hydrogen-Ion Concentration , Immunohistochemistry , Isoenzymes/metabolism , Magnetic Resonance Spectroscopy , Male , Motor Neurons/enzymology , Muscle, Skeletal/enzymology , Muscle, Skeletal/innervation , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Regeneration/physiology , Reverse Transcriptase Polymerase Chain Reaction
20.
Clin Pharmacol Ther ; 69(6): 422-30, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11406739

ABSTRACT

BACKGROUND: A beta(2)-microglobulin adsorption column used for the treatment of dialysis-related amyloidosis removes serum beta(2)-microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin. METHODS: In vivo clearance of digoxin with the beta(2)-microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the beta(2)-microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin. RESULTS: Digoxin concentration was reduced from 1.11 +/- 0.25 ng/mL to 0.57 +/- 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the beta(2)-microglobulin column was about 145 +/- 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed in vitro, and the capacity of the beta(2)-microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 +/- 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the beta(2)-microglobulin column. CONCLUSION: These data suggested that the beta(2)-microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.


Subject(s)
Cardiotonic Agents/isolation & purification , Cardiotonic Agents/poisoning , Digoxin/isolation & purification , Digoxin/poisoning , beta 2-Microglobulin/chemistry , Adsorption , Albumins/metabolism , Animals , Blood Cell Count , Dogs , Female , Hemoperfusion , Humans , Male , Middle Aged , Renal Dialysis , beta 2-Microglobulin/metabolism
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