ABSTRACT
OBJECTIVE: Providing feedback to mammography radiologists and facilities may improve interpretive performance. We conducted a web-based survey to investigate how and why such feedback is undertaken and used in mammographic screening programmes. METHODS: The survey was sent to representatives in 30 International Cancer Screening Network member countries where mammographic screening is offered. RESULTS: Seventeen programmes in 14 countries responded to the survey. Audit feedback was aimed at readers in 14 programmes, and facilities in 12 programmes. Monitoring quality assurance was the most common purpose of audit feedback. Screening volume, recall rate, and rate of screen-detected cancers were typically reported performance measures. Audit reports were commonly provided annually, but more frequently when target guidelines were not reached. CONCLUSION: The purpose, target audience, performance measures included, form and frequency of the audit feedback varied amongst mammographic screening programmes. These variations may provide a basis for those developing and improving such programmes.
Subject(s)
Benchmarking , Breast Neoplasms/diagnostic imaging , Mammography/standards , Mass Screening/standards , Breast Neoplasms/diagnosis , Female , Global Health , Humans , International Cooperation , Internet , Mammography/statistics & numerical data , Mass Screening/statistics & numerical data , Medical Audit , Observer Variation , Surveys and QuestionnairesABSTRACT
Latent fingermarks are invisible to the naked eye and normally require the application of a chemical developer followed by an optical imaging step in order to visualize the ridge detail. If the finger deposition is poor, or the fingermark is aged, it can sometimes be difficult to produce an image of sufficient quality for identification. In this work, we show for the first time how mass spectrometry imaging (in this case time-of-flight secondary ion mass spectrometry, ToF-SIMS) can be used to enhance the quality of partially recovered fingermarks. We show three examples of how chemical imaging can be used to obtain enhanced images of fingermarks deposited on aluminium foil, glass and the handle of a hand grenade compared with conventional development techniques.
ABSTRACT
Allergen challenges induce airway hyperresponsiveness (AHR) and increased airway smooth muscle (ASM) mass in the sensitized rat. Whether the remodeled ASM changes its phenotype is uncertain. We examined, in sensitized Brown Norway rats, the effects of multiple ovalbumin (Ova) challenges on ASM remodeling and phenotype and the role of the epidermal growth factor receptor (EGFR) in these processes. Rats were sensitized with Ova and challenged three times at 5-day intervals with phosphate-buffered saline or Ova and pretreated with the EGFR inhibitor AG-1478 (5 mg/kg) or its vehicle dimethyl sulfoxide. Ova challenges increased ASM mass in all-sized airways and in large airway mRNA expression of smooth muscle myosin heavy chain (sm-MHC), assessed by laser capture. Myosin light chain kinase and the fast myosin isoform SM-B mRNA expressions were not affected. Ova induced AHR to methacholine, and, based on the constant-phase model, this was largely attributable to the small airways and lung derecruitment at 48 h that recovered by 1 wk. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor (HB-EGF) were increased in bronchoalveolar lavage fluid at 48 h after Ova exposure. AG-1478 inhibited AHR and prevented ASM growth. Epithelial gene expression of EGFR, HB-EGF, matrix metalloproteinase (MMP)-9, Gro-α, and transforming growth factor-ß was unaffected by Ova challenges. We conclude that EGFR drives remodeling of ASM, which results from repeated Ova challenge. Furthermore, the latter results in excessive small airway and, to a lesser degree, large airway narrowing to methacholine, and large airway gene expression of contractile protein is conserved.
Subject(s)
Bronchi/pathology , ErbB Receptors/genetics , Muscle, Smooth/pathology , Respiratory Hypersensitivity/pathology , Airway Remodeling/drug effects , Airway Remodeling/immunology , Allergens/immunology , Allergens/pharmacology , Amphiregulin , Animals , Bronchi/drug effects , Bronchi/immunology , Bronchoalveolar Lavage Fluid/chemistry , EGF Family of Proteins , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/immunology , Gene Expression Regulation/drug effects , Glycoproteins/genetics , Glycoproteins/immunology , Heparin-binding EGF-like Growth Factor , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/immunology , Male , Methacholine Chloride/pharmacology , Muscle, Smooth/drug effects , Muscle, Smooth/immunology , Myosin Heavy Chains/genetics , Myosin Heavy Chains/immunology , Ovalbumin/immunology , Ovalbumin/pharmacology , Quinazolines/pharmacology , Rats , Respiratory Hypersensitivity/chemically induced , Respiratory Hypersensitivity/immunology , Respiratory Hypersensitivity/prevention & control , Signal Transduction/drug effects , Smooth Muscle Myosins/genetics , Smooth Muscle Myosins/immunology , Tyrphostins/pharmacologyABSTRACT
Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.â They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.
Subject(s)
Colorectal Neoplasms/diagnosis , Mass Screening/standards , Quality Assurance, Health Care , Early Detection of Cancer , Europe , Evidence-Based Medicine , HumansABSTRACT
OBJECTIVE: The aim of this study was to examine the sensitivity and specificity of screening mammography as performed in Vermont, USA, and Norway. METHODS: Incident screening data from 1997 to 2003 for female patients aged 50-69 years from the Vermont Breast Cancer Surveillance System (116 996 subsequent screening examinations) and the Norwegian Breast Cancer Screening Program (360 872 subsequent screening examinations) were compared. Sensitivity and specificity estimates for the initial (based on screening mammogram only) and final (screening mammogram plus any further diagnostic imaging) interpretations were directly adjusted for age using 5-year age intervals for the combined Vermont and Norway population, and computed for 1 and 2 years of follow-up, which ended at the time of the next screening mammogram. RESULTS: For the 1-year follow-up, sensitivities for initial assessments were 82.0%, 88.2% and 92.5% for 1-, 2- and >2-year screening intervals, respectively, in Vermont (p=0.022). For final assessments, the values were 73.6%, 83.3% and 81.2% (p=0.047), respectively. For Norway, sensitivities for initial assessments were 91.0% and 91.3% (p=0.529) for 2- and >2-year intervals, and 90.7% and 91.3%, respectively, for final assessments (p=0.630). Specificity was lower in Vermont than in Norway for each screening interval and for all screening intervals combined, for both initial (90.6% vs 97.8% for all intervals; p<0.001) and final (98.8% vs 99.5% for all intervals; p<0.001) assessments. CONCLUSION: Our study showed higher sensitivity and specificity in a biennial screening programme with an independent double reading than in a predominantly annual screening program with a single reading. ADVANCES IN KNOWLEDGE: This study demonstrates that higher recall rates and lower specificity are not always associated with higher sensitivity of screening mammography. Differences in the screening processes in Norway and Vermont suggest potential areas for improvement in the latter.
Subject(s)
Breast Neoplasms/diagnostic imaging , Early Detection of Cancer/standards , Mammography/standards , Age Factors , Aged , Female , Humans , Middle Aged , Norway , Professional Practice/standards , Sensitivity and Specificity , VermontABSTRACT
BACKGROUND: Cow's milk is one of the most common causes of food allergy affecting approximately 2.5% of infants in the first years of their life. However, only limited information regarding the allergenic activity of individual cow's milk allergens is available. OBJECTIVE: To analyse the frequency of IgE reactivity and to determine the allergenic activity of individual cow's milk allergens. METHODS: A nitrocellulose-based microarray, based on purified natural and recombinant cow's milk allergens was used to determine IgE reactivity profiles using sera from 78 cow's milk-sensitized individuals of varying ages. The allergenic activity of the individual allergens was tested using patients' sera for loading rat basophil leukaemia cells (RBL) expressing the α-chain of the human receptor FcεRI. RESULTS: Using the microarray and the RBL assay, cow's milk allergens were assessed for frequency of IgE recognition and allergenic activity. Moreover, the RBL assay allowed distinguishing individuals without or with mild clinical reactions from those with severe systemic or gastrointestinal symptoms as well as persons who grew out cow's milk allergy from those who did not. CONCLUSIONS: Component-resolved testing using milk allergen microarrays and RBL assays seems to provide useful additional diagnostic information and may represent a basis for future forms of prophylactic and therapeutic strategies for cow's milk allergy.
Subject(s)
Allergens/immunology , Immunoglobulin E/immunology , Milk Hypersensitivity/diagnosis , Milk Hypersensitivity/immunology , Milk Proteins/immunology , Adolescent , Adult , Aged , Animals , Antigens, CD/immunology , Cell Line, Tumor , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Protein Array Analysis , Rats , Receptors, Fc/immunology , Young AdultABSTRACT
BACKGROUND: Most breast biopsies will be negative for cancer. Benign breast biopsy can cause changes in the breast tissue, but whether such changes affect the interpretive performance of future screening mammography is not known. METHODS: We prospectively evaluated whether self-reported benign breast biopsy was associated with reduced subsequent screening mammography performance using examination data from the mammography registries of the Breast Cancer Surveillance Consortium from January 2, 1996, through December 31, 2005. A positive interpretation was defined as a recommendation for any additional evaluation. Cancer was defined as any invasive breast cancer or ductal carcinoma in situ diagnosed within 1 year of mammography screening. Measures of mammography performance (sensitivity, specificity, and positive predictive value 1 [PPV1]) were compared both at woman level and breast level in the presence and absence of self-reported benign biopsy history. Referral to biopsy was considered a positive interpretation to calculate positive predictive value 2 (PPV2). Multivariable analysis of a correct interpretation on each performance measure was conducted after adjusting for registry, year of examination, patient characteristics, months since last mammogram, and availability of comparison film. Accuracy of the mammogram interpretation was measured using area under the receiver operating characteristic curve (AUC). All statistical tests were two-sided. RESULTS: A total of 2,007,381 screening mammograms were identified among 799,613 women, of which 14.6% mammograms were associated with self-reported previous breast biopsy. Multivariable adjusted models for mammography performance showed reduced specificity (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.73 to 0.75, P < .001), PPV2 (OR = 0.85, 95% CI = 0.79 to 0.92, P < .001), and AUC (AUC 0.892 vs 0.925, P < .001) among women with self-reported benign biopsy. There was no difference in sensitivity or PPV1 in the same adjusted models, although unadjusted differences in both were found. Specificity was lowest among women with documented fine needle aspiration-the least invasive biopsy technique (OR = 0.58, 95% CI = 0.55 to 0.61, P < .001). Repeating the analysis among women with documented biopsy history, unilateral biopsy history, or restricted to invasive cancers did not change the results. CONCLUSIONS: Self-reported benign breast biopsy history was associated with statistically significantly reduced mammography performance. The difference in performance was likely because of tissue characteristics rather than the biopsy itself.
Subject(s)
Biopsy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Breast/pathology , Mammography , Mass Screening/methods , Adult , Aged , Aged, 80 and over , Area Under Curve , Early Detection of Cancer , Female , Humans , Logistic Models , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , ROC Curve , Sensitivity and Specificity , Time FactorsABSTRACT
AIM: To investigate whether sonographic (US) surveillance of polytetrafluoroethylene covered transjugular intrahepatic portosystemic shunts (TIPS) is necessary. MATERIALS AND METHODS: We identified 128 patients who underwent TIPS for complications of portal hypertension between January 2001 and December 2005 at a large tertiary centre. Procedural data were retrospectively analysed. US surveillance of the TIPS was performed at baseline with scheduled follow-up or whenever shunt dysfunction was suspected. Clinical and radiology reports were compared to assess US surveillance of the TIPS. RESULTS: Four hundred and twenty-six US studies were performed, with a median of three per patient (range 1-5). The median follow-up period was 378 days (range 1-1749 days). Twenty-three patients (18%) had baseline US studies performed only whereas 105 (82%) also had follow-up studies. Forty-one (32%) of 128 patients [32 (78%) Wallstent, nine (22%) Viatorr] had Doppler ultrasound abnormalities noted. Venography was performed in all 41 patients. Abnormal venography and elevated hepatic venous pressure gradient (HVPG) was seen in 34 (82.9%) of the 41 patients [29 (85.3%) Wallstent, five (14.7%) Viatorr]. Among the 34 patients, 17 (50%) [13 (76.5%) Wallstent, four (23.5%) Viatorr] had venographic abnormalities noted at the hepatic venous end accompanied by increased HVPG. All four of the Viatorr patients had minor narrowing at the hepatic venous end and HVPG measurements that ranged 3-4 mm Hg above 12 mm Hg. CONCLUSION: Considering the improved patency of covered stents in TIPS, US surveillance may be superfluous after the baseline study.
Subject(s)
Hypertension, Portal/surgery , Portasystemic Shunt, Transjugular Intrahepatic/instrumentation , Stents , Adolescent , Adult , Aged , Coated Materials, Biocompatible , Female , Follow-Up Studies , Humans , Long-Term Care/methods , Male , Middle Aged , Polytetrafluoroethylene , Portasystemic Shunt, Transjugular Intrahepatic/methods , Portography , Postoperative Care/methods , Prosthesis Failure , Retrospective Studies , Ultrasonography, Doppler , Unnecessary Procedures , Vascular PatencyABSTRACT
BACKGROUND: Interval cancers are considered a shortcoming in screening mammography due to less favorable prognostic tumor characteristics compared to screening-detected cancers and consequently a lower chance of survival from the disease. PURPOSE: To describe the mammographic features and prognostic histopathological tumor characteristics of interval breast cancers. MATERIAL AND METHODS: A total of 231 interval breast cancer cases diagnosed in prevalently screened women aged 50-69 years old were examined. Thirty-five percent of the cases were retrospectively classified as missed cancers, 23% as minimal sign, and 42% as true negative (including occult cancers) in a definitive classification performed by six experienced breast radiologists. The retrospective classification described the mammographic features of the baseline screening mammograms in missed and minimal-sign interval cancers, while histopathological reports were used to describe the tumor characteristics in all the subgroups of interval cancers. RESULTS: Fifty percent of the missed and minimal-sign interval cancers combined presented poorly defined mass or asymmetric density, and 26% calcifications with or without associated density or mass at baseline screening. Twenty-seven percent of invasive tumors were <15 mm for missed and 47% for true interval cancers (P<0.001). Lymph node involvement was more common in missed (49%) compared with the true cases (33%, P<0.05). CONCLUSION: Missed interval cancers have less prognostically favorable histopathological tumor characteristics compared with true interval cancers. Improving the radiologist's perception and interpretation by establishing systematic collection of features and implementation of organized reviews may decrease the number of interval cancers in a screening program.
Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography , Aged , Breast Neoplasms/pathology , False Negative Reactions , Female , Humans , Lymph Nodes/diagnostic imaging , Mass Screening , Middle Aged , Retrospective Studies , Time FactorsABSTRACT
The interactions of the 936-species phages sk1, jj50, and 64 with the cell surface of Lactococcus lactis LM0230 were analyzed. Cell envelopes (walls + plasma membrane), cell wall, or plasma membrane from L. lactis ssp. lactis LM0230 each inactivated the phages in vitro. However, other 936-species phages kh and P008, which do not infect strain LM0230, were not inactivated by any of the subcellular fractions. Treating cell walls or plasma membrane with the cell wall hydrolase mutanolysin eliminated inactivation of phage sk1. This suggested that intact cell wall fragments were required for inactivation. A role for plasma membrane in phage sk1 inactivation was further investigated. Boiling, washing in 2 M KCl, 8 M urea, or 0.1 M Na(2)CO(3)/pH 11, or treating the plasma membrane with proteases did not reduce adsorption or inactivation of phage. Adding lipoteichoic acid or antibodies to lipoteichoic acid did not reduce inactivation of phage in a mixture with membrane, suggesting that lipoteichoic acid was not involved. Inactivation by envelopes or cell wall correlated with ejection of DNA from the phage sk1 capsid. Although calcium is required for plaque formation, it was not required for adsorption, inactivation, or ejection of phage DNA by envelopes or cell wall. The results suggest that at least for phages sk1, jj50, and 64, adsorption and phage DNA injection into the host does not require a host membrane protein or lipoteichoic acid, and that cell wall components are sufficient for these initial steps of phage infection.
Subject(s)
Bacterial Adhesion/physiology , Bacterial Proteins/physiology , Bacteriophages , Lactococcus lactis/physiology , Lactococcus lactis/virology , Adsorption , Bacterial Proteins/metabolism , Cell Membrane/metabolism , Cell Membrane/physiology , Lactococcus lactis/growth & development , Lactococcus lactis/metabolism , Membrane Proteins/metabolism , Membrane Proteins/physiology , Viral Plaque Assay , Virus ActivationABSTRACT
PURPOSE: As life expectancy improves for women with breast cancer, more women will be living with symptoms of lymphedema. This study reports the incidence of arm or hand swelling and associated risk factors in women with invasive breast cancer following surgery. METHODS: Data were obtained from baseline and follow-up interviews of women with invasive breast cancer (n = 145), and mammography and pathology records. The Kaplan-Meier method was used to estimate the probability of developing arm or hand swelling over time. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for arm or hand swelling. RESULTS: Of women in this study, 38% self-reported arm or hand swelling. There was a significantly increased risk of arm swelling if women were under 50 years of age, had axillary node dissection, received chemotherapy, worked outside the home, and had a high household income. There was no association of body weight with swelling. A significantly decreased risk of arm swelling was found in women who were on treatment for high blood pressure. After adjustment for nodal dissection, only age had a significant independent effect. CONCLUSIONS: Our study highlights two important areas of future research that could reduce the incidence of lymphedema. There is a need to better understand the role that treatment for high blood pressure may play in protecting women from arm edema. Second, the potential effect of weight as a modifiable lymphedema risk factor needs to be studied in more detail in light of the conflicting results of different studies.
Subject(s)
Breast Neoplasms/surgery , Lymphedema/etiology , Mastectomy/adverse effects , Postoperative Complications/epidemiology , Age Factors , Arm/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Carcinoma in Situ/surgery , Female , Hand/pathology , Humans , Incidence , Interviews as Topic , Logistic Models , Lymphedema/epidemiology , Middle Aged , Risk Factors , SEER Program , Survival Analysis , Time Factors , Vermont/epidemiologyABSTRACT
Antisense phosphorodiamidate morpholino oligomers (PMOs) were tested for the ability to inhibit gene expression in Escherichia coli. PMOs targeted to either a myc-luciferase reporter gene product or 16S rRNA did not inhibit luciferase expression or growth. However, in a strain with defective lipopolysaccharide (lpxA mutant), which has a leaky outer membrane, PMOs targeted to the myc-luciferase or acyl carrier protein (acpP) mRNA significantly inhibited their targets in a dose-dependent response. A significant improvement was made by covalently joining the peptide (KFF)(3)KC to the end of PMOs. In strains with an intact outer membrane, (KFF)(3)KC-myc PMO inhibited luciferase expression by 63%. A second (KFF)(3)KC-PMO conjugate targeted to lacI mRNA induced beta-galactosidase in a dose-dependent response. The end of the PMO to which (KFF)(3)KC is attached affected the efficiency of target inhibition but in various ways depending on the PMO. Another peptide-lacI PMO conjugate was synthesized with the cationic peptide CRRRQRRKKR and was found not to induce beta-galactosidase. We conclude that the outer membrane of E. coli inhibits entry of PMOs and that (KFF)(3)KC-PMO conjugates are transported across both membranes and specifically inhibit expression of their genetic targets.
Subject(s)
Escherichia coli/genetics , Morpholines/pharmacology , Oligonucleotides, Antisense/pharmacology , Acyl Carrier Protein/genetics , Acyl Carrier Protein/metabolism , Amino Acid Sequence , Bacterial Proteins/genetics , Base Sequence , Cell Membrane Permeability , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Escherichia coli/metabolism , Escherichia coli Proteins/chemistry , Gene Expression/drug effects , Genes, Reporter/drug effects , Genes, Reporter/genetics , Genes, myc/drug effects , Genes, myc/genetics , Lac Repressors , Luciferases/antagonists & inhibitors , Luciferases/genetics , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Morpholines/chemistry , Morpholines/metabolism , Morpholinos , Oligonucleotides, Antisense/chemistry , Oligonucleotides, Antisense/metabolism , RNA, Ribosomal, 16S/drug effects , RNA, Ribosomal, 16S/genetics , Repressor Proteins/genetics , beta-Galactosidase/metabolismABSTRACT
The C repeat region of the M6 protein (M6c) from Streptococcus pyogenes was expressed within the Pip bacteriophage receptor on the surface of Lactococcus lactis. M6c was also detected in the culture medium. The pip-emm6c allele was integrated into the chromosome and stably expressed without antibiotic selection. The level of cell-associated surface expression of PipM6c was 0.015% of total cellular protein. The amount of PipM6c on the cell surface was increased about 17-fold by expressing pip-emm6c from a high-copy-number plasmid. Replacing the native pip promoter with stronger promoters isolated previously from Lactobacillus acidophilus increased surface expression of PipM6c from the high-copy-number plasmid up to 27-fold. Concomitantly, the amount of PipM6c in the medium increased 113-fold. The amount of PipM6c did not vary greatly between exponential- and stationary-phase cultures. Western blots indicated that the full-length PipM6c protein and most of the numerous proteolytic products were found only on the cell surface, whereas only one proteolytic fragment was found in the culture medium.
Subject(s)
Antigens, Bacterial , Bacterial Outer Membrane Proteins/metabolism , Bacterial Proteins/metabolism , Bacteriophages/metabolism , Carrier Proteins/metabolism , Lactococcus lactis/metabolism , Membrane Proteins , Receptors, Virus/metabolism , Bacterial Outer Membrane Proteins/chemistry , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins/genetics , Blotting, Western , Carrier Proteins/chemistry , Carrier Proteins/genetics , Lactococcus lactis/genetics , Lactococcus lactis/growth & development , Lactococcus lactis/virology , Plasmids/genetics , Promoter Regions, Genetic/genetics , Protein Engineering , Receptors, Virus/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolismABSTRACT
This study reports on the identification and characterization of a novel abortive infection system, AbiU, from Lactococcus lactis. AbiU confers resistance to phages from the three main industrially relevant lactococcal phage species: c2, 936, and P335. The presence of AbiU reduced the efficiency of plaquing against specific phage from each species as follows: 3.7 x 10(-1), 1.0 x 10(-2), and 1.0 x 10(-1), respectively. abiU involves two open reading frames, abiU1 (1,772 bp) and abiU2 (1,019 bp). Evidence indicates that AbiU1 is responsible for phage resistance and that AbiU2 may downregulate phage resistance against 936 and P335 type phages but not c2 type phage. AbiU appeared to delay transcription of both phage 712 and c2, with the effect being more marked on phage c2.
Subject(s)
Bacterial Proteins/genetics , Bacteriophages/physiology , Lactococcus lactis/virology , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Base Sequence , Cloning, Molecular , DNA, Viral/metabolism , Lactococcus lactis/genetics , Molecular Sequence Data , Plasmids , Sequence Analysis, DNA , Transcription, GeneticABSTRACT
OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.
Subject(s)
Depressive Disorder/drug therapy , Paroxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adolescent , Analysis of Variance , Antidepressive Agents, Tricyclic/therapeutic use , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Imipramine/therapeutic use , Least-Squares Analysis , Male , Paroxetine/adverse effects , Paroxetine/pharmacology , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/pharmacologyABSTRACT
OBJECTIVE: To compare adult psychosocial functioning (PSF) of subjects with prepubertal major depressive disorder (PMDD) to a normal comparison (NC) group. METHOD: PSF of subjects with PMDD (n = 72) and of NC subjects (n = 28) was compared after prospective follow-up to adulthood. These 100 subjects were 90.9% of the baseline 110 subjects who participated in the "Nortriptyline in Childhood Depression: Follow-up Study." Research nurses who were blind to group status conducted telephone interviews using the Longitudinal Interval Follow-up Evaluation (LIFE) to obtain PSF data. RESULTS: At follow-up, the PMDD group was 20.7+/-2.0 and the NC subjects were 20.9+/-2.2 years old. The PMDD subjects were 10.3+/-1.5 years old at baseline. Time between baseline and follow-up was 9.9+/-1.5 years. In the PMDD group, subjects with MDD, bipolar disorder, or substance use disorders during the previous 5 years had significantly worse PSF than NC subjects. These PSF impairments included significantly worse relationships with parents, siblings, and friends; significantly worse functioning in household, school, and work settings; and worse overall quality of life and global social adjustment. CONCLUSIONS: Although combined treatments for PMDD have little scientific basis, multimodality regimens seem prudent until definitive treatment data become available.
Subject(s)
Adaptation, Psychological , Depressive Disorder, Major/psychology , Social Adjustment , Adult , Antidepressive Agents, Tricyclic/therapeutic use , Child , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Female , Follow-Up Studies , Humans , Male , Nortriptyline/therapeutic use , Psychiatric Status Rating Scales , Psychology, ChildABSTRACT
The article describes and analyzes the international survey of fingerprint and laboratory personnel about fingerprint forgery, conducted in four countries during the years 1998 through 1999. The awareness and the attitude of the professionals to the problem of fingerprint forgery was tested.
Subject(s)
Dermatoglyphics , Forensic Medicine , Attitude , Crime , Data Collection , Humans , Reproducibility of Results , Truth DisclosureABSTRACT
OBJECTIVE: To investigate the reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. METHOD: The 1986 version of the KSADS was modified and expanded to include onset and offset of each symptom for both current and lifetime episodes, expanded prepubertal mania and rapid cycling sections, and categories for attention-deficit/hyperactivity disorder and other DSM-IV diagnoses. To optimize diagnostic research, skip-outs were minimized. Subjects participated in the ongoing "Phenomenology and Course of Pediatric Bipolar Disorder" study. Mothers and children were interviewed separately by research nurses who were blind to diagnostic group status. In addition, ratings of off-site child psychiatrists, made from the narrative documentation given for each WASH-U-KSADS item, were compared with research nurse ratings. This work was performed between 1995 and 2000. RESULTS: There was 100% interrater reliability, five consecutive times, as both interviewer and observer after 10 to 15 trials. The kappa values of comparisons between research nurse and off-site blind best-estimate ratings of mania and rapid cycling sections were excellent (0.74-1.00). High 6-month stability for mania diagnoses (85.7%) and for individual mania items and validity against parental and teacher reports were previously reported. CONCLUSIONS: The WASH-U-KSADS mania and rapid cycling sections have acceptable reliability.
Subject(s)
Affective Disorders, Psychotic/diagnosis , Schizophrenia/diagnosis , Affective Disorders, Psychotic/psychology , Child , Female , Humans , Male , Mass Screening , Observer Variation , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Women at risk for inherited breast cancer have been identified for intervention studies through newly diagnosed relatives or from volunteers with a family history. This pilot study tested the use of a mammography registry to identify women at risk. METHOD: Fifty women with first-degree relatives diagnosed as having breast cancer before age 45 were randomly selected from the Vermont Breast Cancer Surveillance System. Thirty-three women (66%) completed a phone interview that included a three-generation family pedigree of breast and ovarian cancers. RESULTS: Fifty-one percent of the women were at higher risk for inherited breast cancer based on the family history. Eighteen percent of the first-degree relatives' breast cancers were pathologically confirmed. CONCLUSION: Mammography registries that collect similar family history data may be used to identify women at risk for inherited breast cancer. Many intervention studies would require improved methods to obtain pathologic confirmation.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Genetic Predisposition to Disease , Mammography , Mass Screening , Registries , Adult , Female , Humans , Interviews as Topic , Mass Screening/methods , Middle Aged , Pilot Projects , Risk Factors , VermontABSTRACT
An unusual, spontaneous, phage sk1-resistant mutant (RMSK1/1) of Lactococcus lactis C2 apparently blocks phage DNA entry into the host. Although no visible plaques formed on RMSK1/1, this host propagated phage at a reduced efficiency. This was evident from center-of-infection experiments, which showed that 21% of infected RMSK1/1 formed plaques when plated on its phage-sensitive parental strain, C2. Moreover, viable cell counts 0 and 4 h after infection were not significantly different from those of an uninfected culture. Further characterization showed that phage adsorption was normal, but burst size was reduced fivefold and the latent period was increased from 28.5 to 36 min. RMSK1/1 was resistant to other, but not all, similar phages. Phage sensitivity was restored to RMSK1/1 by transformation with a cloned DNA fragment from a genomic library of a phage-sensitive strain. Characterization of the DNA that restored phage sensitivity revealed an open reading frame with similarity to sequences encoding lysozymes (beta-1,4-N-acetylmuramidase) and lysins from various bacteria, a fungus, and phages of Lactobacillus and Streptococcus and also revealed DNA homologous to noncoding sequences of temperate phage of L. lactis, DNA similar to a region of phage sk1, a gene with similarity to tRNA genes, a prophage attachment site, and open reading frames with similarities to sun and to sequences encoding phosphoprotein phosphatases and protein kinases. Mutational analyses of the cloned DNA showed that the region of homology with lactococcal temperate phage was responsible for restoring the phage-sensitive phenotype. The region of homology with DNA of lactococcal temperate phage was similar to DNA from a previously characterized lactococcal phage that suppresses an abortive infection mechanism of phage resistance. The region of homology with lactococcal temperate phage was deleted from a phage-sensitive strain, but the strain was not phage resistant. The results suggest that the cloned DNA with homology to lactococcal temperate phage was not mutated in the phage-resistant strain. The cloned DNA apparently suppressed the mechanism of resistance, and it may do so by mimicking a region of phage DNA that interacts with components of the resistance mechanism.