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1.
  • Arnesson, Lars-Gunnar, 1947- (författare)
  • Small breast cancers : Diagnosis, prognostic factors and clinical outcome in a screening population
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Breast cancer ≤ 10 mm together with ductal in situ cancer of the breast (DCIS) today constitute more than 40% of screening detected breast malignancies. Prognostic factors, diagnosis and clinical outcome for invasive breast cancers ≤ 10 mm and local recurrence in DCIS were evaluated.</p><p><strong>Histopathological grading</strong> was done in 248 ductal breast cancers and grade III was correlated to aneuploidy, increased S-phase fraction and receptor negative tumours. Life table analysis showed a significant increase in breast cancer mortality in grade III tumours (p &lt; 0.001).</p><p><strong>Hormone receptors and cytometric variables</strong> were studied in ≤ 10 mm breast cancers. Around 60% of these small cancers were evaluable. Aneuploidy was found in 52% and SPF ≥ 10 in 20%. Mean SPF was 4.8 in diploid and 7.6 in aneuploid tumours. A potentially high risk group with high SPF figures and receptor negative tumours comprise 7% of the patients.</p><p><strong>Diagnostic surgery</strong> was performed in 314 non-palpable breast lesions. Insufficient excisions were observed in 16 cases (5%), mostly in lesions with microcalcifications and in situ cancers ≥ 30 mm in extent. Underestimation of in situ cancers is the main reason for inadequate surgery.</p><p><strong>DCIS</strong> comprises approx 10% of breast malignancies. In 38 cases operated with breast preserving surgery 13% got local recurrence in median 60 months follow-up.</p><p><strong>Recurrence free survival</strong> in patients with ≤ 10 mm breast cancers were evaluated for 324 cases. Only 8% of these patients had adjuvant treatment. Lymph node involvement was found in 9% of screening detected and 20% in clinically detected cancers (p &lt; 0.03). Median prospective follow-up time was 7 years and distant metastases appeared in 8 patients, local recurrence in 3. Life table analysis showed 97% overall distant recurrence free survival, 99% in node negative and 79% in node positive patients (p &lt; 0.001).</p><p>We can today, by grading and cytometric variables, find subgroups with high risk of recurrence after breast cancer surgery in small breast cancers. These are probably the only patients that benefit from adjuvant treatment and need follow-up outside mammography screening. Breast conserving surgery can be performed in the majority of DCIS patients.</p>
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2.
  • Arranz, Belén (författare)
  • Neurobiological aspects of human aging and suicide
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis addresses: 1) The involvement of the monoaminergic and neuropeptidergic neurotransmitter systems in the aging process, and 2) The contribution of these systems in the etiology of an age-related mental disorder: the depressive syndrome. Because of the evidence suggesting the efficacy of the SSRI in the treatment of some age-related symptoms, a comparison study of the binding characteristics of two SSRI, i.e. [3H]paroxetine and [3H]citalopram, to the human brain 5-HT uptake site was included.</p><p>Neurochemical analysis, involving HPLC, binding assays and RIA methods, was performed in several brain regions from 23 control subjects and 18 suicides pooled according to the method of death and the prior existence of depressive symptoms.</p><p>Both [3H]paroxetine and [3H]citalopram were found to label the same number of presynaptic 5-HT binding sites, which is in accordance to their ability to identify the same membrane protein. However, the 15 to 30-fold higher affinity displayed by [3H]paroxetine gives evidence to this SSRI having a more easily accesible binding domain in the 5-HT transport complex than [3H]citalopram, and hence being a better marker of thispresynaptic 5-HT carrier system.</p><p>No statistical differences in either the monoamines 5-HT, NA and DA, their metabolites or the 5-HT binding sites were found between controls and overall suicides. However, a diminished number of 5-HTl D binding sites with advancing age, together with a significant decrease in the number of 5-HTl D binding sites and binding affinity was noticed in the nondepressed and depressed suicides, respectively. These results might indicate the involvement of this novel 5-HT receptor in both some of the physical disturbances present in the elderly population and in the mechanisms underlying the depressive syndrome. Advancing age was also found to be negatively correlated with brain NA, DA and HV A concentrations, thus supporting the increased likelihood of changes in feeding habits and in the hypothalamic-mediated endocrine dysfunctionscommonly observed in senescence.</p><p>With regard to the neuropeptidergic neurotransmitter systems, age-related decreases in gyrus cinguli NPY and CRF concentrations were noted. In addition, although unchanged NPY, SOM and CRF concentrations were observed in the overall suicide group, the HPLC analysis revealed that the depressed suicides showed a different pattern of NPY-LI fragments, which is in agreement with depression being associated with an altered processing or metabolism of the intact NPY molecule.</p>
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3.
  • Bendtsen, Preben, 1956- (författare)
  • Rheumatoid arthritis - patient perception of disease, care, quality of life, coping and well-being : a study from a Swedish health care district
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>During the past decades, the focus of outcome studies in chronic diseases such as rheumatoid arthritis (RA) has changed from a technical and biological preoccupation towards a more patient-concemed psychosocial perspective. The changing paradigm of chronic disease impact has been conceptualised in a number of self-report health status and outcome measurements that have been called 11one of the primary achievements of rheumatology in the 1980s". The overall aim of the study was to make a broad elucidation of the perceived selfMreported impact of rheumatoid arthritis in a representative group of individuals from a health care district, with regard to treatment and care, quality oflife, coping and well-being.</p><p>A total of 321 patients from a health care district in the northern part of Kalmar county, Sweden, with both early/mild and more severe disease were enrolled in the first part of the study, in which the medical records of these individuals were scrutinised for information about previous treatment and care. In the second part of the study, 222 of the initial 321 persons participated in an extensive postal survey exploring perceived impact of RA by self-report.</p><p>The uncertain outcome of RA disease was emphasised by a high frequency of discontinuations of drug therapy due to lack of effect or side-effects. Underlining the lack of a medical cure for RA, more than 40% of the individuals had undergone some kind of surgical procedure due to the disease. The rehabilitation services to individuals with RA appear to be functioning fairly adequately since those still working were employed in administrative work rather than in production. The participants indicated a preference for a good reception by health care workers rather than technically correct care. Only a minority of the patients who had been treated as in-patients felt that they had been involved in the planning of the care. Also, the physicians seemed to underestimate the patients desire for information concerning both medical and social aspects of the disease.</p><p>Quality of life scores exhibited a change for the worse with increasing self-reported functional disability. Physical, psychological and social life domains were fairly highly interrelated and all revealed lower levels with increasing self-reported functional disability. Also, lower levels of well-being were closely associated with a more severe RA disease, in particular loneliness, indolence, tension, security, future-orientation and endurance. Coping and wellMbeing were only weakly interrelated, but individuals who declared an active lifostyle exhibited a better well-being with a higher basic mood, greater fotureorientation and less indolence, loneliness and inferiority. Individuals accepting the RA disease displayed less guilt and tension, and greater endurance and basic mood.</p><p>The study depicts how individuals with RA in a health care district are provided with both the basic treatment and more specialised care in a collaboration between medical and surgical specialists. In general, satisfaction with the care provided was more closely related with clinical signs rather than self-reported functional performance, although the latter might more adequately reflect the perceived need of the patients. Thus, the results support the application of self-reported functional disability assessment in routine clinical rheumatological practice. The study displays methods that measure and quantify the increasing negative psychosocial impact of RA with increasing functional disability. Some evidence was also found supporting the inclusion of coping enhancement elements in health care programmes targeting patients with RA. Consequently, the inclusion of counselling enhancing acceptance of the RA and encouraging decisions about new relevant goals might, at least theoretically, increase well-being in patients with RA.</p>
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4.
  • Berg, Sören, 1954- (författare)
  • Hyaluronan in sepsis : A clinical and experimental study
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Sepsis and septic shock are important causes of morbidity and mortality in the intensive care unit (ICU). Mortality rates in septic shock are estimated to be 40-50%, in spite of modem intensive care. Death is commonly caused by cardiovascular collapse and multiple organ dysfunction syndrome (MODS). Hepatic dysfunction is a common component of MODS, and can have a major impact on prognosis and survival. Sepsis is, among other derangements, also accompanied by disturbed tissue water homeostasis with increased extravasation of water resulting in tissue edema.</p><p>Hyaluronan is an interstitial macromolecule that participates in the regulation of tissue hydration. It is normally present in small concentrations in the blood, and is rapidly cleared from the blood by the liver endothelial cells. The synthesis of hyaluronan can be stimulated by inflammatory mediators. Thus sepsis and hyaluronan turnover could interact in many ways. The aim of the present investigations was to study possible changes in circulating hyaluronan concentrations in relation to sepsis and septic shock.</p><p>Plasma levels of hyaluronan were studied in 44 patients with infections and septic shock. Increased plasma concentrations were found, and the increase correlated to disease severity and outcome. In experimentally induced sepsis in pigs, an increase in circulating concentrations was found, and a relation to hemodynamic instability and outcome was seen. A moderate increase in blood hyaluronan concentrations was seen after surgical trauma in both humans and pigs. Crystalloid infusion therapy also caused a small increase in plasma hyaluronan concentrations in healthy volunteers, probably through an increased washout of interstitial hyaluronan. The hepatic turnover of hyaluronan was studied in septic shock patients. Low extraction ratios at high circulating concentrations were found, suggesting a reduced capacity of hepatic uptake and an increased inflow to the circulation. The kinetics of plasma turnover of hyaluronan were studied in septic and non-septic ICU patients. A prolonged half-life was seen among the septic patients, suggesting a reduced clearance capacity.</p><p>In conclusion, sepsis is accompanied by increased circulating hyaluronan concentrations. The magnitude of the increase seems to correlate to disease severity and outcome. The cause of this increase is suggested to be both reduced hepatic uptake function, and increased input to the circulation. The relative contributions of these mechanisms, and the possible clinical utility of plasma hyaluronan measurements, remain to be determined.</p>
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5.
  • Broqvist, Mats, 1955- (författare)
  • Clinical studies in severe heart failure : neurohormonal, electrolyte and metabolic aspects
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Congestive heart failure is a common and complex syndrome with a poor prognosis. Although heart disease is usually the primary event, the clinical syndrome is characterised by several extra-cardiac manifestations. Neurohormonal activation seems to play a crucial role for these manifestations and the progression of the disease.</p><p>Twenty-seven consecutive patients with acute left ventricular heart failure were found to have increased plasma concentrations of atrial natriuretic peptide, arginine vasopressin and catecholamines, while the renin-angiotensin system was not activated until diuretic therapy was introduced. To counteract this activation it seems suitable to combine the diuretics with an angiotensin-converting enzyme inhibitor.</p><p>Skeletal muscle biopsies were performed in 22 patients participating in the CONSENSUS trial, which was a randomised, double-blind, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on mortality in patients with severe congestive heart failure. The biopsies revealed decreased content of magnesium andpotassium while sodium and water were retained in skeletal muscle. Ventricular arrhythmias occurred frequently. The ventricular arrhythmias seemed to be related to lower serum levels of potassium, but no significant correlations were found to muscle electrolyte content. This may indicate that the ratio of electrolytes across the cell membrane is moreimportant for the development of arrhythmias than changes in the absolute amount of electrolytes are. The muscle biopsies also revealed metabolic derangement with decreased content of energy-rich compunds, such as adenosine triphosphate (ATP), phosphocreatine and glycogen,Treatment with enalapril did not seem to influence these peripheral abnormalities, but some beneficial effect was found regarding the prevalence of ventricular arrhythmias.</p><p>In another 22 patients with severe congestive heart failure, similar signs of energy depletion were found in skeletal muscle biopsies. Nutritional assessment, based on anthropometry and serum protein levels, revealed signs of malnutrition in only two patients which is in contrast to a previous reported prevalence of 30-50 % in patients with severe congestive heartfailure. Long-term oral dietary supplementation, given in a randomised, double-blind and placebo-controlled manner, did not change muscle energy content, neither did exercise tolerance improve. Thus, malnutrition did not seem to be a prerequisite for the metabolic changes found in skeletal muscle. Consequently, routine dietary supplementation does not seem to be indicated in patients with congestive heart failure.</p>
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6.
  • Cederholm, Ingemar, 1951- (författare)
  • Ropivacaine : An experimental and clinical study with special reference to analgesic, circulatory and antiinflammatory effects
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Aims of the study: 1. to compare ropivacaine, a new long-acting amino-amide local anaesthetic drug, and bupivacaine (with/without adrenaline) concerning dermal analgesia and local vascular effects, 2. to design a suitable test procedure to evaluate changes in skin blood flow after intradermal injection of local anaesthetics, 3. to evaluate changes in skin blood flow of various concentrations of ropivacaine with/without adrenaline, 4. to investigate the influence of ropivacaine, bupivacaine, lidocaine, mepivacaine and prilocaine on the production of oxygen metabolites in human polymorphonuclear leukocytes (PMNL) (intra- and extracellular reactions), and 5. to examine the neural blocking characteristics on sensory, motor and sympathetic pathways using ropivacaine for epidural analgesia.</p><p>72 male patients scheduled for transurethral surgery and 50 male volunteers participated in this work. Heparinized blood was obtained from a total of 29 healthy adult blood donors.</p><p>Dermal analgesia was evaluated by pin-prick, skin colour changes by visual inspection, skin blood flow by laser Doppler flowmetry, sensory blockade by pin-prick, motor blockade by a modified Bromage scale, sympathetic blockade by assessments of skin resistance level (SRL) and response (SRR), skin temperature and skin blood flow (laser Doppler flowmetry). Production of oxygen metabolites by PMNLs was measured by luminal-enhanced chemiluminescence (intra- and extracellular reactions).</p><p>Ropivacaine produced significantly longer duration of dermal analgesia, following intradermal injection (0.1 ml, 30-G needle), compared with bupivacaine, in comparable concentrations. Addition of adrenaline increased the duration of both local anaesthetics. Local blanching was more frequent for plain solutions of ropivacaine.</p><p>The effect of drugs on local circulation may well be studied by intradennal injection (0.1 ml, 30-G needle, volar surface, forearms) and recording of changes in skin blood flow (laser Doppler flowmetry). The intradennal injection of a local anaesthetic drug may produce not only a further increase but also a decrease in skin blood flow, if the effect of an intradermal saline injection, causing a very reproducible flow increase, is considered in the evaluation of the net circulatory effect of the tested drug.</p><p>Intradermal injection of lidocaine 1% and bupivacaine 0.75% produced an increase in skin blood flow. Ropivacaine 1% produced a flow similar to saline, while a decrease was seen for ropivacaine 0.75%. Ropivacaine0.5%, 0.375%, 0.25%, 0.125% and 0.063% showed a gradual further reduction in flow, where 0.063% produced a flow similar to adrenaline-injection (5 Jlg/ml) and almost as low as at the untreated control sites. The combination of ropivacaine 1%, 0.5% , 0.25% and adrenaline did not accentuate but instead decreased the vasoconstrictive effect of adrenaline.</p><p>By and large a decrease in response of chemiluminescence for PMNLs was seen with the higher concentrations of the various local anaesthetics. Lidocaine showed a minor decrease even at lower concentrations. Ropivacaine 1000 J.Lg/ml showed a depression of both intra- and extracellular responses that was similar to, and even somewhat more pronounced than lidocaine 1000 J.Lg/ml. This effect could be of great interest e.g. for local antiinflammatory effects by topical administration, but it has to be further investigated. A marked increase for prilocaine (1000 Jlg/ml) in intracellular response accompanied with a reduction in extracellular response was noted.</p><p>Ropivacaine (0.5%, 0.75% with/without adrenaline) 20 ml administered epidurally provided a good sensory blockade and a motor blockade satisfactory for transurethral surgery. The maximum sensory level of analgesia was high, median Th 2-3. The majority of patients had a marked or complete sympathetic blockade in the lower limbs. Besides mild or moderate hypotension, which responded well to treatment with ephedrine, no other serious adverse reactions were seen, Addition of adrenaline did not provide any significant prolongation of the epidural blockade, and did not alter the influence upon the sympathetic blockade nor the hemodynamic changes during onset.</p>
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7.
  • Ekberg, Kerstin, 1948- (författare)
  • An epidemiologic approach to disorders in the neck and shoulders
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Complaints about pain in the locomotor system represent a commonly occuning health problem among working people all over the world. In this context, a series of studies were employed to determine if work organization and psychosocial conditions at work, in addition to physical work load, contribute to the development of disorders in the neck and shoulders. The potentially health-promoting effect of early and active rehabilitation of those already suffering from disorders in the neck and shoulders was also evaluated.</p><p>A first psychophysiological study showed that various stress conditions during monotonous work had limited effects on muscle tension. The interindividual variability in muscle reactions to stress was large, but the results indicate that some individuals may react with a sustained, low-level muscle activity that is associated with pain.</p><p>A cross-sectional study of a sample of a normal working population and a case-control study of patients with disorders in the neck and shoulders revealed a set of work-related core determinants, which appear to be essential component causes for the development of symptoms and signs. Prevalence ratios (PR) were calculated for determinants of early symptoms in the cross-sectional study, and odds ratios (OR) were estimated in the case-control study for determinants of disorders of the neck and shoulders. Repetitive movements demanding precision (PR 1.2 and OR 7.5, respectively), high work pace (PR 1.2 and OR 3.5, respectively), low quality work content (low decision latitude and lqw skill discretion; PR 1.3 and OR 2.6, respectively), and uncertainty about how to perform and-manage the tasks (work-role ambiguity; PR 1.2 and OR 16.5, respectively) were associated with both development of early symptoms, and disorders in the neck and shoulders. The results also show that being a woman (PR 1.3 and OR 11.4, respectively) and I or an immigrant (PR 1.3 and OR 4.9, respectively) imposes a higher risk for developing signs and symptoms in the neck and shoulders, possibly due to selective job-assignment.</p><p>A controlled, two-year follow-up of cohorts of subjects with early and active rehabilitation versus traditional, less active treatment of neck~shoulder disorders respectively, did not support the hypothesis that active rehabilitation, as compared to traditional treatment methods, promotedbetter health, unless work conditions were changed. People who remained on the same job after rehabilitation, independent of type of treatment, had a less positive prognosis (relative risk 3.6) than those who had a changed work situation.</p><p>Further analysis of which factors retained people in long-term sick-leave suggested that work conditions are more important than personality and other individual characteristics in determining the amount of time that will elapse before individuals will resume work after a sickleave. There was no gender-difference in this respect.</p>
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8.
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9.
  • Forastiere, Francesco (författare)
  • Epidemiologic studies of occupational and environmental exposures and cancer of the lung
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In order to study the importance of some less well-known occupational exposures and environmental factors in lung cancer etiology, a series of investigations were conducted in the Latium region of Italy, which includes the city of Rome. Five historical cohort studies were carried out on various occupational groups: power plant workers and merchant seamen with potential exposure to asbestos occupations with exposure to silica dust (silicotics receiving a disability compensation), and occupations withexposure to sulphuric acid mist (soap production workers) and to engine exhaust (taxi drivers). In addition, a case-control study evaluated lung cancer risk among ceramic workers exposed to silica dust, and a correlation study compared lung cancer mortality rates in areas with distinct geological features as a proxy of radon exposure in dwellings. Finally, time trends and geographical differences in lung cancer mortality rates in Italy not due to active smoking (background rates) were estimated to obtain an overall view of the aggregate effect of other factors than active smoking.</p><p>More or less clearly increased risks of lung cancer mortality were observed in the cohorts of power plant workers (SMR=ol. 8, 95% cr~D.77-3.5;9D~ cr~o.ss-3.2), and merchant seamen (SMR~1.7, 95~ CI=l.l-2. 5) 1 probably mainly due to asbestos. An excess lung cancer risk was detected among ceramic workers (OR=2. 0, 95% CI=l.l-3.5); those ceramic workers with silicosis showed an even higher relative risk (0R=3. 9, 95% CI=l. 8-8.3) . Subjects receiving a disability pension for silicosis in the region were also found to have an increased risk of lung cancer (MOR=1.5; 95% CI=l.l-1.9). There was a suggestion of excess risk of lung cancer among workers in the production of soap (SMR=1.7; 95%CI~D.55-3.9; 90~ CI~0.73-3.6), although the limited size of the study precludes any definitive conclusion. Taxi drivers in Rome also appeared to have a slightly increased risk of lung cancer (SMR~1.2, 95~ CI~D.97-1.5), especially those enrolled more recently (SMR~1.4, 95~ CI~l.02-1.9)</p><p>After adjustment for smoking and urbanization, the ecologic study showed a 20% increase in mortality rates for lung cancer in an area with a higher level of background radiation. Indoor radon exposure may be suggested as a potentially important risk factor for lung cancer in that area.</p><p>When differences of time and place in lung cancer death rates not attributable to active smoking were studied, all calculations indicated that the estimated background rates increased in Italy from the period 1956-58 to the period 1987-1989, especially in males. Higher background rates were observed in heavily urbanized areas than in rural areas.</p><p>The overwhelming role in cigarette smoking is well recognized but various environmental factors also play an important role in causing lung cancer. These factors should not be neglected in public health efforts to reduce the risk of lung cancer, especially as they may at times be easier to reduce or eliminate than smoking.</p>
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10.
  • Grodzinsky, Ewa, 1958- (författare)
  • Serological markers in subclinical and clinical gluten enteropathy
  • 1994
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>An enzyme-linked immunosorbent assay (ELISA) has been developed for the measurement of anti-gliadin antibodies (AGA), thereby providing a practical and cheap assay for use in the diagnosis of coeliac disease (CD). Since gliadin is a common food antigen for most people, a large group of apparently healthy blood donors (n=l866) was analysed, as well as children and adults with symptoms more or less suggesting CD. The effects of various cut-offvalues on the sensitivity, specificity and predictive value (PV) of the test were calculated, both alone and together with anti-endomysium antibodies (EMA). A high prevalence value, of at least 1/256 (7!1866), for gluten enteropathy (GE) was found in the blood donor population. Moreover, a high frequency of CD among fanners with diffuse symptoms, conceivably due to a high exposure to gluten by inhalation, was also observed. It was impossible to combine high sensitivity with high specificity for both IgA- and IgG AGA, and vice versa, in adults. A significant increase in the mean lgA AGA level with age was seen when the blood donors were divided into age groups. A positive PV of 18-25% was found for IgA-AGA, depending on how-the cut-off value was defined. For IgG-AGA the positive PV was 0% (0/35) among asymptomatic subjects. IgA-EMA yielded both high specificity and a high positive PV, but a lower sensitivity than IgA-AGA, especially in children younger than 2 years, with signs of CD. When screening for GE in a population with expected low prevalence, measurement of IgA-AGA is suggested as a primary test because of fairly good sensitivity, technical simplicity, and low cost. Sera found to be positive are then re tested with IgA-EMA, which gives a positive PV close to 100%. For populations with a moderate or high expected prevalence for CD, our results indicate that different tests should be used depending on the age of the population studied. In younger children ( &lt; 2 years old) lgA-AGA yielded a high sensitivity (lOO%) and a high specificity (86%). fu older children (&gt; 2 years old) and adults the use of IgA-EMA seems more suitable, because of the high specificity (99-100%) and positive PV (95-100% ). Since, however, the negative PV was not 100%, a negative test result does not exclude CD.</p>
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