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1.
Public Health ; 158: 110-116, 2018 May.
Article in English | MEDLINE | ID: mdl-29653865

ABSTRACT

OBJECTIVES: Asylum seekers to Europe may come from war-torn countries where health systems have broken down, and there is evidence that asylum-seeking children have low coverage of childhood vaccinations, as well as uptake of immunisations in host countries. Such gaps in immunisation have important implications for effective national vaccination programmes. How we approach vaccination in children and adults entering Western Europe, where as a group they face barriers to health services and screening, is a growing debate; however, there are limited data on the vaccination status of these hard-to-reach communities, and robust evidence is needed to inform immunisation strategies. The aim of this study was to explore the vaccination status and needs of asylum-seeking children and adolescents in Denmark. STUDY DESIGN: We conducted a retrospective data analysis of anonymised patient records for asylum-seeking children and adolescents extracted from the Danish Red Cross database. METHODS: We retrospectively searched the Danish Red Cross database for children and adolescents (aged 3 months-17 years) with active asylum applications in Denmark as of October 28, 2015. Data were extracted for demographic characteristics, vaccination status and vaccinations needed by asylum-seeking children presenting to Red Cross asylum centres for routine statutory health screening. RESULTS: We explored the vaccination status and needs of 2126 asylum-seeking children and adolescents. About 64% of the study population were male and 36% were female. Eight nationalities were represented, where 33% of the total of children and adolescents were not immunised in accordance with Danish national guidelines, while 7% were considered partly vaccinated, and 60% were considered adequately vaccinated. Afghan (57% not vaccinated/unknown) and Eritrean (54% not vaccinated/unknown) children were the least likely to be vaccinated of all nationalities represented, as were boys (37% not vaccinated/unknown) compared with girls (27% not vaccinated/unknown) and children and adolescents aged between 12 and 17 years (48% not vaccinated/unknown) compared with 6- to 11-year olds (26%) and 0- to 5-year olds (22%). The health screenings resulted in 1328 vaccinations. The most commonly needed vaccines were diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b, (DTaP/IPV/Hib) which comprised 49% of the vaccines distributed, followed by the pneumococcal vaccine (Prevnar) (28%) and measles, mumps and rubella (MMR) vaccine (23%). CONCLUSIONS: The finding that nearly one-third of asylum-seeking children and adolescents in Denmark were in need of further vaccinations highlights the gaps in immunisation coverage in these populations. These results point to the need to improve access to health services and promote national vaccine programmes targeted at these communities to facilitate vaccination uptake and increase immunisation coverage to reduce the risk of preventable infectious diseases among asylum-seeking children.


Subject(s)
Health Services Needs and Demand , Refugees/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Child , Child, Preschool , Denmark , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies
2.
Parasite Immunol ; 36(8): 388-96, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24962350

ABSTRACT

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data are limited by the relative lack of animal models. This manuscript revises the available information on the immunology of human taeniasis and cysticercosis.


Subject(s)
Meat/parasitology , Swine Diseases/parasitology , Taenia solium/immunology , Taeniasis/veterinary , Animals , Cysticercosis/immunology , Cysticercosis/transmission , Host-Parasite Interactions/immunology , Humans , Life Cycle Stages , Swine , Swine Diseases/immunology , Taenia solium/growth & development , Taeniasis/immunology , Taeniasis/pathology , Taeniasis/transmission
3.
Int J Tuberc Lung Dis ; 26(3): 190-205, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35197159

ABSTRACT

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.


Subject(s)
Latent Tuberculosis , Tuberculosis , Caregivers , Child , Humans , Mass Screening , Reference Standards , Tuberculosis/diagnosis , Tuberculosis/prevention & control
4.
Eur Respir J ; 38(2): 456-64, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21659415

ABSTRACT

Tuberculosis (TB) remains a global health pandemic. Infection is spread by the aerosol route and Mycobacterium tuberculosis must drive lung destruction to be transmitted to new hosts. Such inflammatory tissue damage is responsible for morbidity and mortality in patients. The underlying mechanisms of matrix destruction in TB remain poorly understood but consideration of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will play a central role, owing to their unique ability to degrade fibrillar collagens and other matrix components. Since we proposed the concept of a matrix degrading phenotype in TB a decade ago, diverse data implicating MMPs as key mediators in TB pathology have accumulated. We review the lines of investigation that have indicated a critical role for MMPs in TB pathogenesis, consider regulatory pathways driving MMPs and propose that inhibition of MMP activity is a realistic goal as adjunctive therapy to limit immunopathology in TB.


Subject(s)
Extracellular Matrix/enzymology , Matrix Metalloproteinases/metabolism , Mycobacterium tuberculosis/pathogenicity , Tuberculosis, Pulmonary/enzymology , Gene Expression Profiling , Humans , Lung/diagnostic imaging , Lung/enzymology , Lung/pathology , Matrix Metalloproteinase Inhibitors , Matrix Metalloproteinases/genetics , Monocytes/enzymology , Radiography
5.
Eur Respir J ; 33(1): 134-41, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18715875

ABSTRACT

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.


Subject(s)
Granuloma, Respiratory Tract/etiology , Matrix Metalloproteinase 9/metabolism , Tuberculosis, Pleural/enzymology , Tuberculosis, Pleural/pathology , Adult , Aged , Case-Control Studies , Cohort Studies , Female , Granuloma, Respiratory Tract/enzymology , Granuloma, Respiratory Tract/pathology , Humans , Male , Matrix Metalloproteinase 1/metabolism , Middle Aged , Pleural Effusion/enzymology , Pleural Effusion/etiology , Pleural Effusion/pathology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Tuberculosis, Pleural/complications
6.
Science ; 197(4298): 64-5, 1977 Jul 01.
Article in English | MEDLINE | ID: mdl-194311

ABSTRACT

Dexamethasone and prednisone in physiologic range increased angiotensin converting enzyme 7- to 16-fold in comparison to control in 3 days at maximal stimulation (4 nM steroid) in rabbit alveolar macrophages in culture. The increase was inhibited by actinomycin D (0.1 microng/ml) and 1 micronM cycloheximide, suggesting that de novo transcription and enzyme synthesis are responsible for the increased enzyme activity. This result is evidence for a regulatory mechanism for angiotensin converting enzyme, which is important in blood pressure control.


Subject(s)
Dexamethasone/pharmacology , Macrophages/enzymology , Peptidyl-Dipeptidase A/metabolism , Prednisone/pharmacology , Animals , Cell Line , Cells, Cultured , Colchicine/pharmacology , Dactinomycin/pharmacology , Enzyme Induction/drug effects , Peptidyl-Dipeptidase A/biosynthesis , Pulmonary Alveoli/cytology , Rabbits
7.
J Clin Invest ; 67(4): 1151-60, 1981 Apr.
Article in English | MEDLINE | ID: mdl-6259212

ABSTRACT

To enable its immunohistologic localization, angiotensin converting enzyme (EC 3.4.15.1) from human lung was solubilized by trypsinization and purified approximately 2,660-fold to apparent homogeneity from a washed lung particulate fraction. The specific activity of pure enzyme was estimated to be 117 mumol/min per mg protein with the substrate hippuryl-l-histidyl-l-leucine. Consistent with previously described lung enzyme studies, catalytic activity was strongly inhibited by EDTA, O-phenanthroline, SQ 20,881, and SQ 14,225 and increased by CoCl(2). SQ 20,881 was a somewhat more potent inhibitor than SQ 14,225, unlike rabbit lung enzyme. The Michaelis constant (K(m)) with hippuryl-l-histidyl-l-leucine was 1.6 mM. The molecular weight was estimated at 150,000 from sucrose density gradient centrifugation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a single polypeptide chain estimated at 130,000 daltons. Rabbit antibody to human lung enzyme was prepared by parenteral administration of pure angiotensin-converting enzyme in Freund's adjuvant. Rabbit antibody to human lung angiotensin-converting enzyme appeared to crossreact weakly with the rabbit enzyme and strongly inhibited the catalytic activity of the enzymes from human serum, lung, and lymph node. The specificity of the rabbit antibody and purity of the final human lung enzyme preparation was suggested by the single precipitin lines obtained by radial double immunodiffusion, and by the coincidence of enzyme catalytic activity and immunoreactivity on polyacrylamide gel electrophoresis, with both relatively pure and highly impure enzymes. Generally applicable sensitive analysis of acrylamide gels for immunoreactivity (and subsequently for any other activity) by use of intact gel slices in radial double immunodiffusion was devised. Human lung enzyme was very tightly bound to and catalytically active on anti-human enzyme antibody covalently bound to Sepharose 4B, and could not be readily dissociated without inactivation. Antibody to human lung angiotensin converting enzyme has permitted tissue localization of the enzyme, which appears to be clinically useful in diseases associated with abnormal abundance of angiotensin-converting enzyme in tissues, such as sarcoidosis.


Subject(s)
Lung/enzymology , Peptidyl-Dipeptidase A/isolation & purification , Angiotensin-Converting Enzyme Inhibitors , Antibodies , Electrophoresis, Polyacrylamide Gel , Humans , Immunodiffusion , Peptidyl-Dipeptidase A/immunology
8.
Clin Microbiol Infect ; 23(3): 141-146, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27665703

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe is more prevalent among migrants than the native population. The impact of the recent increase in migration to EU and EEA countries with a low incidence of TB (<20 cases per 100Ā 000) on MDR-TB epidemiology is unclear. This narrative review synthesizes evidence on MDR-TB and migration identified through an expert panel and database search. A significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes. Although concerns have been raised around 'health tourists' migrating for MDR-TB treatment, numbers are probably small and data are lacking. Migrants experience significant barriers to testing and treatment for MDR-TB, exacerbated by increasingly restrictive health systems. Screening for latent MDR-TB is highly problematic because current tests cannot distinguish drug-resistant latent infection, and evidence-based guidance for treatment of latent infection in contacts of MDR patients is lacking. Although there is evidence that transmission of TB from migrants to the general population is low-it predominantly occurs within migrant communities-there is a human rights obligation to improve the diagnosis, treatment and prevention of MDR-TB in migrants. Further research is needed into MDR-TB and migration, the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-base is urgently needed to inform guidelines for effective approaches for MDR-TB management in migrant populations in Europe.


Subject(s)
Disease Transmission, Infectious/prevention & control , Emigration and Immigration , Infection Control , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/transmission , Antitubercular Agents/therapeutic use , Diagnostic Tests, Routine , Europe/epidemiology , Humans , Medication Adherence , Tuberculosis, Multidrug-Resistant/diagnosis
9.
J Immunol Methods ; 309(1-2): 115-9, 2006 Feb 20.
Article in English | MEDLINE | ID: mdl-16386754

ABSTRACT

Matrix metalloproteinases (MMPs) are implicated in the immunopathology of numerous infectious diseases. High risk samples such as those generated after infection with Mycobacterium tuberculosis require filter sterilization for safe analysis of MMP concentrations. Here, we report that commercial filter membranes may cause artefacts by binding MMPs. Anopore 0.2 microM membrane filtration reduced MMP-1 concentrations to undetectable levels by zymography and Western blotting. Polypropylene 0.45 microM filtration removed some MMP-1, while Polysulphone, Durapore and Bio-inert 0.2 microM membranes did not remove MMP-1. Anopore filtration also removed all MMP-7 and -9 activity, suggesting that the conserved MMP catalytic domain binds the membrane. This study demonstrates the importance of selecting the appropriate filter in MMP analysis to avoid incorrectly excluding MMP involvement in infection-related immunopathology.


Subject(s)
Matrix Metalloproteinases/analysis , Micropore Filters , Binding Sites , Blotting, Western , Bronchi/enzymology , Bronchi/microbiology , Cells, Cultured , Communicable Diseases/enzymology , Communicable Diseases/microbiology , Epithelial Cells/cytology , Epithelial Cells/enzymology , False Negative Reactions , Humans , In Vitro Techniques , Matrix Metalloproteinase 1/analysis , Matrix Metalloproteinase 1/isolation & purification , Matrix Metalloproteinase 7/analysis , Matrix Metalloproteinase 7/isolation & purification , Matrix Metalloproteinases/isolation & purification , Mycobacterium tuberculosis/pathogenicity , Sterilization/methods
10.
J Leukoc Biol ; 70(3): 447-54, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11527995

ABSTRACT

Monocyte phagocytosis of pathogens or inflammatory debris leads to chemokine secretion and heralds the influx of leukocytes to the site of injury. Persistent chemokine secretion can lead to tissue damage. However, the mechanisms by which phagocytosis regulates chemokine synthesis remain poorly understood. As a first step, we have studied regulation of interleukin (IL) 8 gene expression after interaction with zymosan or latex. IL-8 secretion was consistently one- or twofold higher after incubation with zymosan than with latex. Nuclear factor (NF) kappaB translocation to the nucleus was induced by zymosan but not latex, indicating that its translocation is dependent on the nature of the phagocytic stimulus. NFkappaB activation coincided with IkappaBalpha degradation but had no effect on processing of NFkappaB1/p105, the precursor of the NFkappaB protein p50. The NFkappaB inhibitor gliotoxin abrogated zymosan-induced IL-8 synthesis in peripheral blood monocytes, further demonstrating that the induction of IL-8 mRNA by zymosan is NFkappaB dependent. SB203580 inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway significantly decreased zymosan-induced IL-8 mRNA accumulation. Inhibitors of protein kinases A and C or tyrosine kinases had no significant effect on zymosan-induced IL-8 synthesis. These data indicate that p38 MAPK and NFkappaB are critical in controlling zymosan-induced IL-8 secretion.


Subject(s)
I-kappa B Proteins , Interleukin-8/biosynthesis , Monocytes/immunology , Phagocytosis , Zymosan/pharmacology , Cell Line , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , DNA-Binding Proteins/metabolism , Enzyme Inhibitors/pharmacology , Gliotoxin/pharmacology , Humans , Interleukin-8/genetics , MAP Kinase Signaling System/drug effects , Monocytes/drug effects , NF-KappaB Inhibitor alpha , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Protein Kinase C/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , RNA, Messenger/biosynthesis , Transcriptional Activation
11.
Probl Tuberk Bolezn Legk ; (8): 50-3, 2005.
Article in Russian | MEDLINE | ID: mdl-16209022

ABSTRACT

The present-day problems in tuberculosis control are associated with a difficulty in detecting Mycobacterium tuberculosis (MBT) in due time and in determining its drug sensitivity by conventional microbiological assays. The determination of the drug sensitivity of MBT takes much time from 2 weeks to 3 months, which fails to initiate and perform specific therapy timely. Molecular genetic techniques, including biochip analysis, yield results in 24-48 hours, which solves the problem of choosing and initiating adequate antibacterial therapy in the shortest possible time after tuberculosis is diagnosed. To assess the situation associated with the prevalence of rifampicin-resistant tuberculosis, by using the biochip analysis, the authors have examined 501 patients with tuberculosis who live in the Kyrghyz Republic. Drug resistance has been found in 40.3% of the examinees. At the same time, their primary and secondary drug resistance is 25.7 and 61.8%, respectively. In tuberculosis patients living in Kyrghyzstan, rifampicin resistance of MBT is more frequently due to mutations in 531 (59.2%), 526 (20.8%), and 516 (8.0%) codons in the rpoB gene.


Subject(s)
Antibiotics, Antitubercular/pharmacology , DNA, Bacterial/analysis , Drug Resistance, Bacterial/genetics , Microchip Analytical Procedures , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Rifampin/pharmacology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Codon , Genes, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mutation , Polymerase Chain Reaction , Recurrence , Time Factors
12.
Matrix Biol ; 21(1): 103-10, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11827797

ABSTRACT

In tuberculosis, matrix metalloproteinase (MMP) secretion is involved in leukocyte migration to sites of infection but in excess may contribute to tissue destruction. We demonstrate that human monocytic THP-1 cells and primary monocytes secrete MMP-1 (52 kD collagenase) when phagocytosing live, virulent M. tuberculosis but not inert latex. The magnitude of MMP-1 secretion was approximately 10-fold less when compared to MMP-9 (92 kD gelatinase) secretion. MMP-1 secretion was also relatively delayed (detected at 24 h vs. 4 h). M. tuberculosis, zymosan or latex stimulate similar TIMP-1 secretion within 8 h and increasing over 24 h. MMP-1/9 secretion was decreased by inhibitors of protein kinase (PK) C, PKA or tyrosine kinases (PTK) in a concentration-dependent manner. In contrast, TIMP-1 secretion was not affected by PKC or PTK blockade and only somewhat reduced by high level PKA inhibition. In summary, M. tuberculosis-infected monocytes secrete MMP-1 at lower concentrations than MMP-9 and such MMP secretion is regulated by multiple upstream signalling pathways which do not control TIMP-1 secretion. Divergent effects of i on MMP and TIMP secretion from monocytes may be important in influencing matrix degradation in vivo.


Subject(s)
Carbazoles , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Monocytes/microbiology , Mycobacterium tuberculosis/physiology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Cell Line , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Genistein/pharmacology , Humans , Indoles/pharmacology , Monocytes/drug effects , Monocytes/metabolism , Naphthalenes/pharmacology , Protein Kinase C/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrroles/pharmacology , Signal Transduction/physiology , Zymosan/pharmacology
13.
Medicine (Baltimore) ; 69(6): 325-31, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2233230

ABSTRACT

A small clinically distinct group of patients with widespread tissue granulomata are described. The principal presenting symptoms are malaise, fever, and weight loss, although a wide variety of complaints are documented. Pulmonary involvement is uncommon. The granulomata are noncaseating with a few multinucleate giant cells and some surrounding chronic inflammatory infiltrate. There is no evidence of an associated arteritis. The disease has a relapsing and remitting course and although it may require treatment with immunosuppressive drugs, particularly if the kidneys are involved, the prognosis is relatively good. We propose that this entity be called granulomatous syndrome of unknown origin. The characteristics that set this syndrome apart from the other granulomatous vasculitides are discussed. The current limited understanding of granuloma formation does not allow us to propose a definite etiology for this condition. It is emphasized that it is not helpful to encompass it within a label of sarcoidosis. First, it may only serve to confuse the doctor in assessing and treating this very particular group of patients. Secondly, it may hinder future attempts to understand the different pathogenetic mechanisms underlying the various conditions in which granulomata may arise.


Subject(s)
Granuloma/pathology , Adolescent , Adult , Chronic Disease , Diagnosis, Differential , Female , Follow-Up Studies , Granuloma/immunology , Humans , Kidney Diseases/pathology , Liver Diseases/pathology , Male , Middle Aged , Skin Diseases/pathology , Splenic Diseases/pathology , Syndrome
14.
Cancer Epidemiol Biomarkers Prev ; 9(12): 1357-67, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11142422

ABSTRACT

This study investigated the potential association between organochlorine exposure and breast cancer using stored sera collected from 1973 through 1991 from the Janus Serum Bank in Norway. Breast cancer cases were ascertained prospectively from among 25,431 female serum bank donors. A total of 150 controls were matched to cases by birth dates and dates of sample collection. One g of serum per subject was analyzed for a total of 71 organochlorine compounds. For 6 pesticides [B-hexachlorocyclohexane, heptachlor epoxide, oxychlordane, trans-nonachlor, p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, and p, p'-2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and 26 individual polychlorinated biphenyl (PCB) congeners there were >90% of samples over the limit of detection. There was no evidence for higher mean serum levels among cases for any of these compounds, nor any trend of increasing risk associated with higher quartiles of exposure. The remaining compounds (including dieldrin) were analyzed with respect to the proportion of cancer cases and controls having detectable levels; no positive associations were noted in these analyses. Our study did not confirm the recent findings of a Danish study of increased concentrations of dieldrin in the serum of breast cancer cases. The evidence to date on the association between serum organochlorines is not entirely consistent, but there is accumulating evidence that serum levels of p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and total PCBs are not important predictors for breast cancer in the general population. Studies to date have not been able to evaluate whether exposure to highly estrogenic, short-lived PCB congeners increases breast cancer risk, nor have they fully evaluated the risk associated with organochlorine exposure in susceptible subgroups or at levels above general population exposure, including women with occupational exposure.


Subject(s)
Adenocarcinoma/blood , Breast Neoplasms/blood , Insecticides/blood , Adenocarcinoma/chemically induced , Adolescent , Adult , Age Factors , Blood Banks/statistics & numerical data , Breast Neoplasms/chemically induced , Case-Control Studies , Female , Humans , Middle Aged , Norway , Polychlorinated Biphenyls/blood , Prospective Studies , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Regression Analysis
15.
Neuropsychologia ; 24(3): 411-5, 1986.
Article in English | MEDLINE | ID: mdl-3736824

ABSTRACT

Based on a study with seven nonfluent aphasics, Grossman (Neuropsychologia 18, 299-308, 1980) advanced the 'central processor' claim that the mental representation of hierarchical linguistic structure is functionally equivalent to processing hierarchically-structured, nonlinguistic forms. Grossman reported that both abilities are compromised in Broca's aphasia. We attempted to replicate this effect with eight nonfluent aphasics using essentially the same task requiring the reconstruction from memory of stick designs. With the addition of controls for post-stroke interval, responding hand and gender, only the female aphasics had difficulty executing the hierarchical arrangement of visual-spatial materials. This sex difference disputes the strong form of the central processor hypothesis and supports the view that females may be more likely to possess partial noncomplementarity of specialization (dependence on the same hemisphere for selective language and spatial functions).


Subject(s)
Aphasia, Broca/psychology , Aphasia/psychology , Dominance, Cerebral , Space Perception , Adult , Aphasia, Broca/physiopathology , Brain/physiopathology , Female , Humans , Language , Male , Memory , Middle Aged , Sex Characteristics , Sex Factors
16.
Am J Med ; 69(3): 408-10, 1980 Sep.
Article in English | MEDLINE | ID: mdl-6251722

ABSTRACT

The cellular localization of the elevated angiotensin-converting enzyme (ACE) in the spleen of a patient with Gaucher's disease was examined by immunofluorescence using an antibody prepared against highly purified human lung enzyme. Intense ACE-specific cytoplasmic fluorescence was observed in Gaucher cells, but not in various controls, indicating the localization of large quantities of enzyme in these cells. These results and the demonstrated capability of mononuclear phagocytes for marked induction of this enzyme suggest the possibility that induction of active synthesis of ACE in Gaucher cells may be responsible for the elevated enzyme levels in the serum and spleen of patients with Gaucher's disease.


Subject(s)
Fluorescent Antibody Technique , Gaucher Disease/enzymology , Peptidyl-Dipeptidase A/analysis , Spleen/enzymology , Humans
17.
Am J Med ; 75(2): 233-6, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6309003

ABSTRACT

Serum angiotensin-converting enzyme was elevated in patients with hyperthyroidism (72 +/- 31 nmol/minute/ml, n = 12, p less than 0.001) but not in patients with hypothyroidism (38 +/- 3, n = 3) or thyroiditis (26, n = 1), and was positively correlated in 23 patients with serum thyroxine concentration (r = 0.60, p less than 0.01) and triiodothyronine resin uptake (r = 0.56, p less than 0.01). Triiodothyronine failed to enhance the synthesis of angiotensin-converting enzyme in rabbit alveolar macrophages or in human monocytes in culture, suggesting that the increased serum enzyme is a consequence of an effect other than increased angiotensin-converting enzyme synthesis. Hyperthyroidism should be considered in the evaluation of serum angiotensin-converting enzyme for the diagnosis and management of sarcoidosis.


Subject(s)
Hyperthyroidism/enzymology , Peptidyl-Dipeptidase A/blood , Dexamethasone/pharmacology , Humans , Hypothyroidism/enzymology , Macrophages/drug effects , Monocytes/drug effects , Peptidyl-Dipeptidase A/biosynthesis , Thyroiditis/enzymology , Thyroxine/blood , Triiodothyronine/pharmacology
18.
Int J Radiat Oncol Biol Phys ; 44(4): 789-99, 1999 Jul 01.
Article in English | MEDLINE | ID: mdl-10386635

ABSTRACT

PURPOSE/OBJECTIVE: To develop and disseminate the American Brachytherapy Society (ABS) recommendations for the clinical quality assurance and guidelines of permanent transperineal prostate brachytherapy with 125I or 103Pd. METHODS AND MATERIALS: The ABS formed a committee of experts in prostate brachytherapy to develop consensus guidelines through a critical analysis of published data supplemented by their clinical experience. The recommendations of the panels were reviewed and approved by the Board of Directors of the ABS. RESULTS: Patients with high probability of organ-confined disease are appropriately treated with brachytherapy alone. Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental external beam radiation therapy (EBRT). Patient selection guidelines were developed. Dosimetric planning of the implant should be carried out for all patients before seed insertion. A modified peripheral loading is preferred. The AAPM TG-43 recommendations requiring a change in prescription dose for 125I sources should be universally implemented. The recommended prescription doses for monotherapy are 145 Gy for 125I and 115-120 Gy for 103Pd. The corresponding boost doses (after 40-50 Gy EBRT) are 100-110 Gy and 80-90 Gy, respectively. Clinical evidence to guide selection of radionuclide (103Pd or 125I) is lacking. Post implant dosimetry and evaluation must be performed on all patients. It is suggested that the dose that covers 90% (D90) and 100% (D100) of the prostate volume and the percentage of the prostate volume receiving the prescribed dose (V100) be obtained from a dose-volume histogram (DVH) and reported. CONCLUSION: Guidelines for appropriate patient selection, dose reporting, and improved quality of permanent prostate brachytherapy are presented. These broad recommendations are intended to be technical and advisory in nature, but the ultimate responsibility for the medical decisions rests with the treating physician. This is a constantly evolving field, and the recommendations are subject to modifications as new data becomes available.


Subject(s)
Brachytherapy/methods , Prostatic Neoplasms/radiotherapy , Biopsy , Brachytherapy/standards , Humans , Iodine Radioisotopes/therapeutic use , Male , Palladium/therapeutic use , Patient Selection , Postoperative Care , Prostatic Neoplasms/pathology , Quality Assurance, Health Care , Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , United States
19.
Int J Radiat Oncol Biol Phys ; 40(4): 1001-5, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9531387

ABSTRACT

PURPOSE: To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. METHODS AND MATERIALS: Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. RESULTS: Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. CONCLUSION: While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.


Subject(s)
Brachytherapy/standards , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage/standards , Brachytherapy/methods , Health Care Surveys , Humans , Iodine Radioisotopes/therapeutic use , Male , Palladium/therapeutic use , Quality Assurance, Health Care , Radioisotopes/therapeutic use , Radiometry/methods , Radiopharmaceuticals/therapeutic use , United States
20.
Int J Radiat Oncol Biol Phys ; 40(2): 461-5, 1998 Jan 15.
Article in English | MEDLINE | ID: mdl-9457836

ABSTRACT

PURPOSE: To help establish standards of care for transperineal interstitial permanent prostate brachytherapy (TIPPB) by obtaining data regarding current clinical practice among the most experienced TIPPB brachytherapists in the United States. METHODS AND MATERIALS: The 70 brachytherapists who performed the greatest number of TIPPB cases in 1995 in the U.S. were surveyed. Each received a comprehensive four page questionnaire that included sections on training and experience, patient and isotope selection criteria, manpower, technique, and follow-up. Thirty-five (50%) surveys were ultimately returned after three mailings and follow-up phone calls. The cumulative experience of the 35 respondents represented approximately 45% of the total TIPPB volume in the U.S. for 1995. Respondents included 29 from the private sector and six from academic programs. RESULTS: The median physician experience with TIPPB was reported as 4.9 years. Each performed an average of 73 TIPPB procedures in 1995 (range 40-300). This represented an increase in volume for most (74%) of the respondents. Sixty-three percent of the respondents attended a formal training course, 54% had TIPPB-specific residency training, and 31% had been proctored (16 had received two or more types of training experience). The most commonly reported selection criteria for implant alone was on Gleason score < or = 7, PSA < 15, < or = Stage T2a, and gland size < or = 60 cc, although no clear consensus was found. Fifty-four percent considered a history of TURP to be a relative contraindication, while 34% considered TURP to have no impact on patient selection. Eighty-six percent of respondents combine brachytherapy with external beam radiation in an average of 32% of their patients. Boosts were given with both 125I prescribed to 120 Gy (75%) or 103Pd to 90 Gy (50%). Sixty percent reported using a Mick applicator, 46% prefer using preloaded needles, and (11%) use both techniques. Real-time imaging was usually performed with ultrasound (94%); most included fluoroscopy (60%). Definitions of PSA control varied widely. CONCLUSIONS: TIPPB clinical practice in the U.S. demonstrates similarities in technique, but differences in patient selection and definitions of biochemical control. It is, therefore, incumbent on those beginning TIPPB programs to carefully review the specific practice details of those institutions with a broad experience.


Subject(s)
Brachytherapy/standards , Health Care Surveys , Practice Patterns, Physicians'/standards , Prostatic Neoplasms/radiotherapy , Brachytherapy/methods , Brachytherapy/statistics & numerical data , Humans , Male , Patient Selection , Practice Patterns, Physicians'/statistics & numerical data , Radioisotopes/therapeutic use , United States
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