ABSTRACT
BACKGROUND: As demand for total shoulder arthroplasty (TSA) rises, containing costs will become increasingly important. We hypothesize that performing ambulatory TSA procedures results in significant cost savings. METHODS: A model was created to evaluate cost savings. Hospital stay length and cost, pain control method and cost, and number of annual outpatient TSA procedures were estimated based on literature. RESULTS: Estimated cost savings per patient were $747 to $15,507 (base case $5594), total annual savings of $4.1M to $349M (base case $82M), and ten-year savings of $51M to $5.4B (base case $1.1B). CONCLUSION: Ambulatory TSA procedures result in significant cost savings.
ABSTRACT
OBJECTIVE: We compared digital tomosynthesis (TOMO) and chest CT in terms of assessing the sizes of nodules located in zones where evaluation by simple radiography is limited. METHODS: A total of 48 images comprising phantom nodules of four sizes in six different locations were used. Nodule size measurement errors for measurements using TOMO and CT images compared with the actual size from each observer were calculated. The inter- and intraobserver repeatability of the measured values and the agreement between the two techniques were assessed using the method described by Bland and Altman. RESULTS: The mean measurement errors for all of the nodules and four observers were -0.84 mm [standard deviation (SD), 0.60 mm] on TOMO and -0.18 mm (SD, 0.71 mm) on CT images. The mean measurement errors for the different observers ranged from -1.11 to -0.55 mm for TOMO and from -0.39 to 0.08 mm for CT. Assessing the agreement between nodule size measurements using TOMO and CT resulted in mean measurement errors of -0.65 mm, with a 95% limit of agreement of -2.53 to 1.22 mm for comparison of TOMO with CT. CONCLUSION: Our results suggest that nodule sizes obtained using TOMO and chest CT are comparable, even for nodules located in areas where the size measurement is limited on simple radiography. ADVANCES IN KNOWLEDGE: TOMO and CT can be used interchangeably, even for nodules located in a blind area on simple radiography.
Subject(s)
Lung Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Phantoms, Imaging , Radiography, Thoracic/methods , Solitary Pulmonary Nodule/diagnostic imaging , Tomography, X-Ray Computed/methods , Humans , ROC CurveABSTRACT
OBJECTIVES: The purpose of this study was to review radiological images of patients with Paragonimus westermani (PW) that simultaneously involved the chest and abdomen. METHODS: Our study included four patients with serologically and histopathologically confirmed paragonimiasis. Abdomen CT (n=3) and chest CT (n=3) scans were available, and abdominal wall ultrasonography was performed in all patients. We retrospectively reviewed the clinical, radiological and histopathological findings of these patients. RESULTS: The most common abdominal CT findings were ascites and intraperitoneal or abdominal wall nodules. Low-attenuated serpentine lesions of the liver were another common and relatively specific feature. CONCLUSION: Radiologists should consider the possibility of PW when these abdominal CT findings are noted, especially with pleural effusion or subpleural nodules in patients with initial abdominal symptoms.
Subject(s)
Abdomen , Paragonimiasis/diagnosis , Thoracic Diseases/diagnosis , Tomography, X-Ray Computed , Abdomen/diagnostic imaging , Adult , Animals , Female , Humans , Male , Middle Aged , Paragonimiasis/diagnostic imaging , Paragonimus westermani , Pleural Effusion/diagnostic imaging , Radiography, Abdominal , Radiography, Thoracic , Thoracic Diseases/diagnostic imaging , UltrasonographyABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy and safety of performing transthoracic needle biopsy (TNB) under combined fluoroscopy and CT guidance using a C-arm cone-beam CT (CBCT) system. METHODS: We evaluated the diagnostic accuracy and safety of performing TNB using a C-arm CBCT system. We retrospectively evaluated 99 TNB cases performed in 98 patients using a C-arm CBCT system with an 18-gauge automated cutting needle. We reviewed the diagnostic accuracy according to the size and depth of the lesion, incidence of complications, additional treatment for complications, procedure time, number of needle passes per biopsy and radiation dose. RESULTS: The final diagnoses revealed 72 malignant and 27 benign lesions. The overall malignancy sensitivity, malignancy specificity and diagnostic accuracy were 95.8%, 100% and 97.0%, respectively, and those for small pulmonary nodules <20 mm in size were 94.1%, 100% and 96.6%, respectively. There was no significant difference in the correct diagnosis of malignancy according to lesion size (p = 0.634) or depth (p = 0.542). For benign lesions, a specific diagnosis was obtained in 14 cases (51.9%). TNB induced complications in 19 out of 99 procedures (19.2%), including pneumothorax (16.2%), immediate haemoptysis (2.0%) and subcutaneous emphysema (1.0%). Among these, four patients with pneumothorax required chest tube insertion (2.0%) or pig-tail catheter drainage (2.0%). The mean procedure time, number of needle passes and radiation doses were 11.9 ± 4.0 min, 1.2 ± 0.5 times and 170.0 ± 67.2 mGy, respectively. CONCLUSION: TNB using a C-arm CBCT system provides high diagnostic accuracy with a low complication rate and a short procedure time, particularly for small pulmonary nodules.
Subject(s)
Biopsy, Needle/methods , Cone-Beam Computed Tomography , Lung Diseases/pathology , Lung Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle/adverse effects , Female , Fluoroscopy , Humans , Lung Diseases/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , ThoraxABSTRACT
OBJECTIVE: To characterise the prognosis and identify factors contributing to mortality in patients with tuberculous destroyed lung (TDL). DESIGN: Following a retrospective review of clinical data and radiographic findings, 169 patients with TDL were enrolled in this study. All patients were graded on a 4-point scale (field score 1-4) based on the extent of destroyed lung parenchyma on chest radiography. RESULTS: The mean patient age was 64 years (range 33-90); 103 (61%) were male. The median number of hospitalisations was 1 (range 0-11) during follow-up, with a mean duration of 31 months (range 0-172). Pneumonia developed in 96 patients (57%), while 50 patients (30%) developed acute respiratory failure requiring mechanical ventilation, 37 (22%) haemoptysis, 24 (14%) spontaneous pneumothorax and 22 (13%) reactivation of tuberculosis. Overall mortality was 28% (47/169), with a median survival of 39 months (range 0-176) after diagnosis. TDL-related mortality was 19% (32/169), and a field score ≥ 3 was the only independent predictor of shorter survival based on a Cox proportional hazards model (HR 3.520, 95%CI 1.51-8.20, P = 0.004). CONCLUSION: TDL has a poor prognosis, particularly in patients with more extensive lung destruction.
Subject(s)
Lung/pathology , Tuberculosis, Pulmonary/mortality , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Hemoptysis/microbiology , Humans , Kaplan-Meier Estimate , Lung/microbiology , Lung/physiopathology , Male , Middle Aged , Oxygen Inhalation Therapy , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality , Pneumothorax/microbiology , Proportional Hazards Models , Republic of Korea/epidemiology , Respiration, Artificial , Respiratory Insufficiency/microbiology , Respiratory Insufficiency/mortality , Respiratory System Agents/therapeutic use , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Survival Rate , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/therapyABSTRACT
AIM: To retrospectively evaluate the computed tomography (CT) appearances of novel influenza A (H1N1) infection. MATERIALS AND METHODS: Chest CT images obtained at clinical presentation in 21 patients (eight men, 13 women; mean age, 37 years; age range, 6-82 years) with confirmed novel influenza A (H1N1) infection were assessed. The radiological appearances of pulmonary parenchymal abnormalities, distribution, and extent of involvement on initial chest CT images were documented. The study group was divided on the basis of age [group 1, patients <18 years old (n=8); group 2, patients ≥ 18 years old (n=13)]. Medical records were reviewed for underlying medical conditions and laboratory findings. The occurrence of recognizable CT patterns was compared for each group using the images from the initial CT examination. RESULTS: The most common CT pattern observed in all patients was ground-glass attenuated (GGA) lesions (20/21, 95%). Bronchial wall thickening (9/21, 43%) was the second most common CT finding. Other common CT findings were consolidation (6/21, 29%), pleural effusion (6/21, 29%), pneumothorax or pneumomediastinum (5/21, 24%), and atelectasis (5/21, 24%). Among these, atelectasis and pneumomediastinum (pneumothorax) were only observed in group 1. The GGA lesions showed predilections for diffuse multifocal (10/20, 50%) or lower zone (8/20, 40%) distribution. Involvement of central lung parenchyma (12/20, 60%) was more common than a mixed peripheral and central pattern (6/20, 30%) or a subpleural pattern (2/20, 10%) at the time of presentation. Patchy GGA lesions were more frequent (18/20, 90%) than diffuse GGA lesions, and 75% (15/20) of these lesions had a bronchovascular distribution. Bilateral disease was present in all patients with GGA lesions. Bronchial wall thickening was predominantly centrally located and the distribution of the consolidation was non-specific. CONCLUSION: The predominantly centrally located GGA lesions, with common multifocal or bilateral involvement, peribronchovascular distribution, and patchy appearance are the more distinctive CT findings of novel influenza A (H1N1) infection. Pneumomediastinum and atelectasis resulting from this disease are more common in young patients under the age of 18 years.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human/diagnostic imaging , Adolescent , Adult , Aged , Child , Disease Outbreaks , Female , Humans , Influenza, Human/epidemiology , Korea/epidemiology , Male , Middle Aged , Tomography, X-Ray Computed , Young AdultSubject(s)
Adenoma , Alveolar Epithelial Cells/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung/diagnostic imaging , Lymphangioleiomyomatosis/diagnostic imaging , Adenoma/diagnostic imaging , Adenoma/pathology , Adult , Alveolar Epithelial Cells/pathology , Diagnosis, Differential , Female , Humans , Hyperplasia/diagnostic imaging , Hyperplasia/pathology , Lung/pathology , Lung Neoplasms/pathology , Lymphangioleiomyomatosis/pathology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: To gain insight into the process of labor and the effects of labor on placental gene expression, we performed a microarray analysis to identify the differentially expressed transcripts that may participate in labor onset and progression. METHODS: We compared expression profiles in placentas from 16 women who underwent elective non-labored cesarean section and from seven women who underwent vaginal delivery. Oligonucleotide probes representing 55,000 genes were used to measure gene expression. Differential gene expression was evaluated using the Student's t-test and fold change assessment and reverse transcription PCR was used to validate the differentially expressed genes. RESULTS: A total of 351 genes were found to be differentially expressed between the two groups. Among these differentially expressed genes, 344 genes were up-regulated and seven were down-regulated. These differentially expressed genes involved 15 categories including genes involved in stress response, immune response, cell death, coagulation, and blood vessel development which are considered to be most closely associated with the inflammatory response that characterizes labor. CONCLUSION: A total of 351 differentially expressed genes of 15 categories were found in the placentas of the vaginal delivery group, indicating a diversity of gene expression alteration and complexity in the labor process. These gene expression changes could be a cause of labor onset and progress or simply an effect of labor.
Subject(s)
Labor Onset/metabolism , Placenta/metabolism , Adult , Cesarean Section , Female , Gene Expression Profiling , Humans , Infant, Newborn , Oligonucleotide Array Sequence Analysis , Pregnancy , Principal Component Analysis , Term BirthABSTRACT
Recent electrophysiological work shows that chronic lithium treatment increases long-term potentiation (LTP) in neurons of the hippocampus, and LTP is thought to be the major neurophysiological basis for the development of learning and memory. This suggests that lithium might enhance learning and memory. Available studies have mainly assessed memory using aversive conditioning paradigms, but very little is available on the effect of lithium on learning. Since lithium may diminish anxiety or negative affect in adult rats, which would hinder aversive learning, the present study used three different positive reinforcement spatial cognitive tasks to determine whether chronic lithium affects learning. Each task differed in complexity, in the type of learning required, and in the reward received. For 4 weeks prior to, and throughout all learning assessments, rats had continual access to lithium chow or to a control chow diet. After 4 weeks' access to their designated chow diet, rats began conditioning in the hole-board spatial discrimination or T-maze delayed alternation tasks in a counterbalanced fashion. They immediately began conditioning in the opposite task once completing the first. This was then followed with social place-preference conditioning, after 24-h isolation from their home-cage social partner. Chronic lithium increased learning in all three paradigms, regardless of the reward received. Indeed, both food and social interaction supported enhanced learning. Thus the learning effect was not merely due to an effect of lithium on food palatability. Importantly, clinically relevant serum lithium levels were evidenced at the time of testing. Lithium also marginally enhanced memory as well. Thus chronic lithium treatment may improve learning and memory in Alzheimer's disease, and do so not only by blocking the formation of beta-amyloid and neurofibrillary tangles as suggested by previous research, but also by enhancing mechanisms involved in basal learning and memory formation, such as hippocampal synaptic plasticity.
Subject(s)
Antipsychotic Agents/administration & dosage , Learning/drug effects , Lithium Compounds/administration & dosage , Analysis of Variance , Animals , Antipsychotic Agents/blood , Behavior, Animal/drug effects , Body Weight/drug effects , Drug Administration Schedule , Lithium Compounds/blood , Male , Maze Learning/drug effects , Neuropsychological Tests , Rats , Rats, Sprague-Dawley , Sodium/blood , Time FactorsABSTRACT
OBJECTIVES: Measurement of fetal urine production may provide a means of evaluating amniotic fluid volume, which is difficult to measure directly, and predicting fetal hypoxia. Although there have been some reports on fetal urine production, most of these have used two-dimensional (2D) ultrasonography to measure bladder volume. Three-dimensional (3D) ultrasonography is, however, known to be superior to 2D ultrasonography in some organ volume measurements. Thus, we undertook this study to measure bladder volumes using 3D ultrasonography and to establish a nomogram of fetal urine production rate (UPR) according to gestational age (GA). METHODS: One hundred and fifty-four women with a normal singleton pregnancy at 24 to 40 weeks' gestation were enrolled in this cross-sectional study. The women had no medical or obstetric complications affecting amniotic fluid volume. Fetal bladder volume was measured using 3D ultrasound imaging and Virtual Organ Computer-aided AnaLysis (VOCAL) with a rotational angle of 30 degrees and manual surface tracing technique. Bladder volume was measured two or three times within a 5-10-min interval and fetal UPR was calculated from serial measurements. When measurements were performed more than twice, we used the mean rate of calculated UPRs. UPR was then plotted against GA to establish the nomogram. RESULTS: Fetal UPR increased with GA from a median value of 7.3 mL/h at 24 weeks' gestation to 71.4 mL/h at term, and could be calculated from GA using the formula: Ln(UPR) = - 6.29582 + (0.43924 x GA) + (0.000432 x GA2), r2 = 0.63, P = 0.0046. Growth percentiles of UPR according to age are presented. CONCLUSIONS: Fetal UPR can be easily measured by 3D ultrasound assessment of bladder volume. This modality may be a promising alternative to conventional methods of amniotic fluid volume measurement such as amniotic fluid index and single deepest pocket, and might be an alternative option for predicting fetal hypoxia.
Subject(s)
Amniotic Fluid , Urinary Bladder/diagnostic imaging , Urine , Cross-Sectional Studies , Female , Fetal Development , Fetal Weight , Gestational Age , Humans , Imaging, Three-Dimensional/methods , Pregnancy , Reference Values , Ultrasonography, Prenatal/methods , Urinary Bladder/anatomy & histology , Urinary Bladder/embryologyABSTRACT
OBJECTIVE: The purpose of this study was to determine whether concentrations of C-reactive protein (CRP) in umbilical cord plasma at birth were elevated in neonates with sepsis, an inflammatory lesion of the umbilical cord (funisitis) or who were born to mothers with microbial invasion of the amniotic cavity. METHODS: Umbilical cord plasma was collected at birth from 313 singleton preterm neonates (20-35 weeks of gestation). The results of amniotic fluid culture performed within 5 days of birth, the occurrence of congenital neonatal sepsis and the presence of funisitis were assessed. Amniocentesis was performed in 152 patients within 5 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. RESULTS: The median cord plasma CRP concentration was significantly higher in neonates with a positive amniotic fluid culture than in those with negative culture (median 245.9 (range 11.6-4885.5) ng/ml vs. median 44.3 (range 2.3-7401.8) ng/ml; p < 0.001), in those with congenital proven sepsis than in those without this complication (median 789.5 (range 20.4-2584.3) ng/ml vs. median 41.5 (range 1.3-7401.8) ng/ml; p < 0.005) and in neonates with funisitis than in those without funisitis (median 403.8 (range 4.9-10897.4) ng/ml vs. median 31.0 (range 1.3-7401.8) ng/ml; p < 0.001). The sensitivity of CRP in the identification of amniotic fluid infection, neonatal sepsis and funisitis was similar to that of interleukin-6 (> 17.5 pg/ml). However, the specificity of CRP in the identification of neonatal sepsis and funisitis was significantly higher than that of interleukin-6 (74% vs. 69%, p < 0.05; 83% vs. 76%, p < 0.01). CONCLUSION: Umbilical cord plasma CRP concentrations were elevated in patients with amniotic fluid infection, congenital neonatal sepsis and funisitis.
Subject(s)
C-Reactive Protein/metabolism , Chorioamnionitis/diagnosis , Fetal Blood/metabolism , Infant, Newborn, Diseases/diagnosis , Sepsis/diagnosis , Adult , Amniotic Fluid/microbiology , Biomarkers/blood , Female , Humans , Infant, Newborn , Predictive Value of Tests , Pregnancy , Sensitivity and SpecificityABSTRACT
OBJECTIVE: The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with preterm labor and intact membranes. STUDY DESIGN: Amniocentesis was performed in 206 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. The diagnosis of intraamniotic inflammation was made in patients with a negative amniotic fluid culture on the basis of amniotic fluid concentrations of interleukin-6 (>2.6 ng/mL, derived from receiver operating characteristic curve analysis). Statistical analysis was conducted with contingency tables and survival techniques. RESULTS: Intra-amniotic inflammation (negative amniotic fluid culture but elevated amniotic fluid interleukin-6) was more common than intra-amniotic infection (positive amniotic fluid culture regardless of amniotic fluid interleukin-6 concentration; 21% [44/206 women] vs 10% [21/206 women]; P <.001). The amniocentesisto-delivery interval was significantly shorter in patients with intra-amniotic inflammation than in patients with a negative culture and without an inflammation (median, 20 hours [range, 0.1-2328 hours] vs median, 701 hours [range, 0.1-3252 hours], respectively; P <.0001). Spontaneous preterm delivery of <37 weeks was more frequent in patients with intra-amniotic inflammation than in those with a negative culture and without inflammation (98% vs 35%; P <.001). Patients with intra-amniotic inflammation had a significantly higher rate of adverse outcome than patients with a negative culture and without intra-amniotic inflammation. Adverse outcomes included clinical and histologic chorioamnionitis, funisitis, early preterm birth, and significant neonatal morbidity. There were no significant differences in the rate of adverse outcomes between patients with a negative culture but with intra-amniotic inflammation and patients with intra-amniotic infection (positive culture regardless of amniotic fluid interleukin-6 concentration). CONCLUSION: Intra-amniotic inflammation/infection complicates one third of the patients with preterm labor (32%; 65/206 women), and its presence is a risk factor for adverse outcome. The outcome of patients with microbiologically proven intra-amniotic infection is similar to that of patients with intra-amniotic inflammation and a negative amniotic fluid culture. We propose that the treatment of patients in preterm labor be based on the operational diagnosis of intra-amniotic inflammation rather than the diagnosis of intra-amniotic infection because the latter diagnosis cannot be undertaken rapidly.
Subject(s)
Chorioamnionitis/physiopathology , Extraembryonic Membranes/physiology , Obstetric Labor, Premature , Amniocentesis , Amnion/microbiology , Amniotic Fluid/microbiology , Chorioamnionitis/diagnosis , Chorioamnionitis/epidemiology , Delivery, Obstetric , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Prevalence , Risk Factors , Time FactorsABSTRACT
OBJECTIVE: A positive fetal fibronectin result in cervicovaginal fluid is a powerful predictor of preterm delivery and is considered a marker for upper genital tract infection (ie, intrauterine infection). Treatment with antimicrobial agents is being considered in patients with a positive fetal fibronectin test of cervico/vaginal fluid. This study was undertaken to determine the frequency and clinical significance of intra-amniotic infection/inflammation in patients with a positive fetal fibronectin. STUDY DESIGN: A total of 1709 pregnant women (gestational age, 23-31 weeks) were screened for cervical fetal fibronectin. Patients with a positive fibronectin were offered amniocentesis for the diagnosis of intra-amniotic infection and treatment with antibiotics. Amniocentesis was performed in 58 patients with a positive fibronectin test (>50 ng/mL). Amniotic fluid was cultured for aerobic/anaerobic bacteria and mycoplasmas. Polymerase chain reaction assay for Ureaplasma urealyticum was performed. Interleukin-6 concentrations were measured by a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: None of the patients with a positive fibronectin had a positive amniotic fluid culture. U urealyticum was detected in 1 case (1.8%) with the polymerase chain reaction assay. Amniotic fluid IL-6 was elevated (>2.5 ng/mL) in 5.3% of patients (3/57 patients); all of these patients delivered preterm neonates. There was no relationship between amniotic fluid IL-6 and cervical fibronectin concentration (r = 0.14;P: >.1). Patients who delivered preterm (<34 weeks) had higher median amniotic fluid IL-6 and cervical fetal fibronectin concentrations than those patients who delivered after 34 weeks (IL-6: median, 2.1 ng/mL [range, 0.1-25.3 ng/mL] vs median, 0.3 ng/mL [0.03-2.4 ng/mL]; P <.05; fibronectin: median, 509 ng/mL [260->1000 ng/mL] vs median, 155 ng/mL [50-889 ng/mL]; P <.01). CONCLUSION: Intra-amniotic infection was detected in 1.8% of cases with a positive fibronectin in the cervical fluid; intra-amniotic inflammation was present in 5.3% of cases. All patients with a positive fetal fibronectin and intra-amniotic inflammation delivered preterm neonates.
Subject(s)
Cervix Uteri/metabolism , Chorioamnionitis/epidemiology , Chorioamnionitis/physiopathology , Fibronectins , Glycoproteins/metabolism , Adult , Amniotic Fluid/chemistry , Amniotic Fluid/microbiology , Female , Humans , Infant, Newborn , Infant, Premature , Interleukin-6/analysis , Osmolar Concentration , Pregnancy , Ureaplasma urealyticum/isolation & purificationABSTRACT
OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.
Subject(s)
Amniocentesis , Amniotic Fluid/enzymology , Matrix Metalloproteinase 8/metabolism , Obstetric Labor, Premature/etiology , Adult , Amniotic Fluid/microbiology , Case-Control Studies , Female , Humans , Interleukin-6/metabolism , Odds Ratio , Osmolar Concentration , Pregnancy , Pregnancy Trimester, Second , Ribonuclease, Pancreatic/metabolism , Risk Factors , Ureaplasma urealyticum/isolation & purificationABSTRACT
We used ligand binding to ascertain whether the pharmacological actions of RO 25-6981 [(R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol] match those of other NR2B (epsilon2) subunit specific agents. RO 25-6981 inhibited binding of 125I-MK801 [iodo-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate] to receptors made from NR1a/epsilon2 but not NR1a/epsilon1. Increasing the concentration of spermidine did not change the efficacy of RO 25-6981 and minimally changed the IC(50) value. Chimeric epsilon1/epsilon2 receptors demonstrated that the structural determinants for high affinity actions of RO 25-6981 were contained completely within the first 464 amino acids, but no receptor retained wildtype features when the size of the epsilon2 component was decreased further. Epsilon1Q336R receptors were more inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand binding assays but not in functional assays. Selected mutations of epsilon2E200 and epsilon2E201 also decreased the sensitivity of receptors to ifenprodil and RO 25-6981. These results suggest that RO 25-6981 shares structural determinants with ifenprodil and other modulators in the NR2B subunit.
Subject(s)
Excitatory Amino Acid Antagonists/pharmacology , Phenols/pharmacology , Piperidines/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Brain/drug effects , Brain/metabolism , Cell Line , Dizocilpine Maleate/pharmacology , Dopamine Antagonists/pharmacology , Excitatory Amino Acid Antagonists/metabolism , Haloperidol/pharmacology , Humans , Kinetics , Mice , Mutation , Phenols/chemistry , Phenols/metabolism , Piperidines/chemistry , Piperidines/metabolism , Protein Structure, Tertiary , Radioligand Assay , Rats , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/chemistry , Receptors, N-Methyl-D-Aspartate/genetics , Recombinant Fusion Proteins/metabolism , Spermidine/pharmacologyABSTRACT
Somatic mutations in the p53 tumor suppressor gene are the most common genetic alterations found in human malignancies. In the present study, we studied 36 primary human breast carcinomas, using a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing analysis of exons 2 through 9 for the presence of p53 gene mutations. Six of 36 (17%) breast cancers contained mutations within the core domain of the p53 protein responsible for sequence-specific DNA binding (codons 102-292); all 5 missense mutations clustered between codons 240 and 291 (codons 240, 243, 250, 285, and 291), whereas one nonsense mutation occurred at codon 199. By using recombinant PCR in vitro mutagenesis, we introduced point mutations at codons 199 from Gly to stop (gly199stop), 240 from Ser to Ile (ser240Ile), 250 from Pro to Ala (pro250ala), 285 from Glu to Lys (glu285lys), and 291 from Lys to Asn (lys291asn), and all the p53 sequences were subcloned into the CMVneoBam vector under the control of the cytomegalovirus (CMV) promoter. To test whether the mutants p53 were functionally wild-type (wt) or mutant, we transfected them to p53-null Saos-2 cells with a reporter plasmid containing a p53-responsive element, and performed chloramphenicol acetyltransferase (CAT) assay. Transient CAT assay for transcriptional activation revealed that one group, including gly199stop, ser240ile, glu285lys, and lys291asn, abolished the transcriptional activity, whereas the other group, including pro250ala, retained stronger transcriptional transactivation activity than that of wt p53.
Subject(s)
Breast Neoplasms/genetics , Genes, p53/genetics , Transcriptional Activation/genetics , Tumor Suppressor Protein p53/metabolism , Adult , Aged , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Electrophoresis , Female , Gene Expression Regulation, Neoplastic/genetics , Genes, Reporter/genetics , Genetic Vectors/genetics , Humans , Immunohistochemistry , Middle Aged , Mutagenesis, Site-Directed , Point Mutation , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Sequence Analysis, DNA , Tumor Cells, Cultured , Tumor Suppressor Protein p53/geneticsABSTRACT
With two ultrasonographic and two CT films of three cases of thyroid tuberculosis, we evaluate the ultrasonographic and CT findings and correlate them with the pathologic findings. They are demonstrated as heterogeneous hypoechoic mass on ultrasonogram and peripheral-enhancing low-density abscess on CT scan with regional lymphadenopathy. Ultrasonography (US) and CT can help the diagnosis of thyroid tuberculosis.
Subject(s)
Thyroid Diseases/diagnostic imaging , Tuberculosis, Endocrine/diagnostic imaging , Adult , Female , Humans , Middle Aged , Radiography , UltrasonographyABSTRACT
Haloperidol inhibits NMDA receptors with higher affinity for NMDA receptors composed of NR1/2B compared with NR1/2A. To assess whether the clinical effects of haloperidol and other antipsychotic agents are mediated through this site on NMDA receptors and to examine structure activity relationships at this site, we examined the ability of a variety of drugs with neuroleptic actions to inhibit NMDA receptor function. Many antipsychotic agents inhibit 125I-MK 801 binding to the NMDA receptor with IC50 values in the micromolar range. The rank order of potency for inhibition of binding to adult rat forebrain was trifluperidol (TFP) > clozapine = fluphenazine = reduced haloperidol = spiperone = trifluoperazine = butaclamol >> pimozide = risperidone = sulpiride. These findings match the molecular biological specificity of the agents, with trifluperidol having a marked preference for NR1/2B (epsilon2) receptors. Mutations at epsilon2E201, which alter the effects of haloperidol, also decrease the affinity of TFP but not other modulators, showing that the effect of TFP but not other modulators is mediated by this residue of the NMDA receptor. The present results demonstrate that while TFP acts on NMDA receptors in a manner similar to haloperidol, other antipsychotic agents do not share the specific pharmacological properties of this action, suggesting that their clinical mechanism is not mediated by this receptor.
Subject(s)
Antipsychotic Agents/pharmacology , Butyrophenones/pharmacology , Receptors, N-Methyl-D-Aspartate/drug effects , Animals , Dizocilpine Maleate/metabolism , Iodine Radioisotopes , Radioligand Assay , Rats , Receptors, N-Methyl-D-Aspartate/metabolism , Recombinant Proteins/drug effects , Recombinant Proteins/metabolism , Spermidine/metabolismABSTRACT
To determine whether lesions in the prefrontal cortex (PFC) alter the activity of midbrain dopamine (DA) neurons, single unit recordings were made from DA neurons in control and lesioned rats. PFC lesions, obtained by local injection of ibotenic acid into the medial PFC, had no effect on either firing rate or bursting activity of DA neurons in the ventral tegmental area (VTA). However, the number of spontaneously active DA neurons in the VTA was significantly decreased. In the substantia nigra (SN), the same lesions increased the firing rate and had no effect on either the bursting activity of the number of active DA cells. These results suggest that PFC lesions alter the activity of DA neurons. However, VTA and SN DA neurons may respond differently to PFC lesions.
Subject(s)
Mesencephalon/physiology , Neurons/physiology , Prefrontal Cortex/drug effects , Animals , Excitatory Amino Acid Agonists , Ibotenic Acid , Injections, Intraventricular , Male , Patch-Clamp Techniques , Prefrontal Cortex/pathology , Rats , Rats, Sprague-Dawley , Receptors, Dopamine/physiologyABSTRACT
The effects of inhibiting monoamine oxidase (MAO) A and B on metabolism and uptake of serotonin (5-HT) in serotonergic synaptosomes were studied. To avoid contamination by extrasynaptosomal MAO, synaptosomes were separated from other components of rat brains by discontinuous sucrose density gradient centrifugation. Kinetic analysis of 5-HT uptake demonstrated that 5-HT was selectively transported into serotonergic synaptosomes through the high affinity 5-HT uptake process. Selectivity of the uptake and subsequent deamination of 5-HT within serotonergic synaptosomes were confirmed using selective and non-selective 5-HT and norepinephrine (NE) uptake inhibitors. MAO inhibitor analysis of 5-HT deamination occurring within serotonergic synaptosomes indicated that, at physiologically relevant concentrations of 5-HT, MAO A deaminates 5-HT, maintaining a low cytoplasmic concentration of 5-HT. When the cytoplasmic concentration of 5-HT is increased above physiologically relevant levels by the inhibition of MAO A, MAO B becomes active. [( 14)C] 5-HT uptake into synaptosomes was reduced by decreasing the V( max) of [(14)C] 5-HT uptake. One mechanism for a decrease in the V(max) could be the increase in the cytoplasmic concentration of 5-HT.