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Population-based cervical screening with a 5-year interval in The Netherlands. Stabilization of the incidence of squamous cell carcinoma and its precursor lesions in the screened population.

OBJECTIVE: To evaluate the outcome of population-based cervical screening at 5-year intervals. STUDY DESIGN: Results from the west region of the Netherlands (population 2 million) were used. The 1995-2000 round was compared with the first 2 years of the second (2001-2002). All results were prospectively collected in a central database. Positive cytologies and histoscores per 1,000 screened for preinvasive squamous cervical intraepithelial neoplasia (CIN) lesions and invasive squamous cell carcinoma were calculated. RESULTS: In the first round, 378,081 women were screened; in the second round, 100,561 women were screened. In both rounds the youngest screenees had the highest cytoscores. Cytoscores in the first round did not differ significantly from those in the second. The histoscore for CIN 1 and 2 was 1.42 per 1,000 in the first round and 1.18 per 1,000 (NS, P < .01) in the second. The histoscore for CIN 3 was 2.07 per 1,000 in the first round and 2.13 per 1,000 (NS, P < .01) in the second. Histoscores for invasive squamous cell carcinoma remained virtually the same (0.16 per 1,000 in the first, 0.14 per 1,000 in the second round). CONCLUSION: Population-based screening at 5-year intervals in the Netherlands may result in stabilization of positive cytology and of the incidence of CIN and (histologic) invasive squamous cell carcinoma. The program seems more cost effective than that of 2 decades ago, with a screening interval of 3 years.

Adult↗

The importance of complete screening for amyloid fibril type and systemic disease in patients with amyloidosis in the respiratory tract.

BACKGROUND: Patients with symptomatic thoracic involvement by amyloidosis are virtually all of AL-type, and have historically been divided into systemic and localised disease, a subdivision that helps predict outcome and aids management. Assessment and classification of amyloid has evolved in recent years to include a variety of tests, including radiolabelling of the serum amyloid P component (SAP scan) to assess anatomical distribution and immunohistochemical studies to assess fibril subtypes. Furthermore, CT scanning is now a frequent investigation for the diagnosis of thoracic disease. We wished to determine the value of these investigations on the management of such patients with amyloidosis. METHODS: Clinicopathological data, including immunohistochemical analysis, CT scans and SAP scan results, were retrospectively reviewed from patients presenting with amyloidosis in the respiratory tract. These were then analysed to determine their impact on classification and prognosis. RESULTS: Seventeen patients over ten years were identified, one case being related to metastatic medullary carcinoma of the thyroid. Of the remaining 16 cases, one was shown to have hereditary amyloid of transthyretin-type (TTR) on immunohistochemistry, altering management. The remaining 15 cases were AL-type, with 6 cases being classified as localised and 9 cases as systemic, after evaluation for serum and/or urine monoclonal products, cardiac involvement via echocardiography, plasma cell abnormalities on bone marrow examination, CT scan and SAP scan. 3/3 patients with localised AL-type disease had a negative SAP scan, whilst 3/5 patients with systemic AL-type disease had a positive scan. SAP scan of the patient with TTR-type disease provided information on extent of disease and supported the diagnosis by the pattern of distribution. Using CT scans to discriminate between localised and systemic disease showed a significant association with mortality at 2 years (p = 0.03). CONCLUSION: Although the majority of symptomatic patients with pulmonary amyloidosis have AL-type disease, immunohistochemical confirmation is necessary in order not to miss rarer subtypes with completely different treatment regimes. Furthermore, a comprehensive evaluation, including SAP scan and CT scan of the thorax, in conjunction with echocardiography, bone marrow, serum and urine studies, needs to be undertaken in order to achieve maximum accuracy with regard to localised and systemic disease.

Aged↗

Surgical education and Internet-based simulation: The World Virtual University.

The new means and modalities of communication and information technologies have significantly revolutionized access to surgical education. The introduction of the Internet information highway into mainstream clinical practice as an information sharing medium offers a wide range of opportunities to healthcare professionals. High-speed Internet broadcasting allows the display of high-quality full-screen videos. Access to surgical procedures through the Internet already plays a major role in continuing medical education nowadays and will undoubtedly be gaining grounds in the future. WebSurg.com, the World Virtual University, a web-based surgical university, is dedicated to minimally invasive laparoscopic surgery. Using brand-new multimedia data, the electronic university provides thorough descriptions of over 150 procedures in minimal access surgery and 265 videos of surgical interventions. Such a teaching tool recreates all the prerequisites and requirements of a traditional School of Medicine, incorporating the manifold standpoints of world-renowned experts about specific topics and hands-on hints in various surgical specialities. Following the evolution of technologies, recent advances have made it possible to display items of Websurg.com on handheld devices (personal data/digital assistance also known as PDAs, Pocket PCs, and smart phones). Integrating all these elements into a unique World Virtual University, Websurg.com epitomizes the concept of a unified academic center providing teaching and tutorials administered by international experts. The Internet assuredly contributes to the worldwide diffusion of scientific information in an easy and user-friendly way.

Journal Article↗

Prospective analysis of strategies for diagnosing renovascular hypertension.

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.

Adult↗

[Screening programs for sporadic colorectal carcinoma].

In developed countries colorectal cancer (CRC) is the second most frequent organ malignancy of both genders. According to the world statistics Czech Republic occupies the top position in incidence of this disease. Approximately 75% of all CRC are the sporadic CRC in subjects with negative family or personal history of the disease. The low (average) risk factor in these subjects is age over 50 years, from which the incidence of CRC nearly doubles in each decade. The following options of screening are available for these subjects: 1. faecal occult blood test (FOBT), 2. flexible sigmoidoscopy, 3. combination of both previous procedures, 4. colonoscopy, 5. virtual colonography. FOBT is the mostly used programme in asymptomatic subjects over age 50 at one-year or at least two-years intervals. In FOBT-positive persons colonoscopy is considered the optimal diagnostic and in the case of polyps also therapeutic method. Prospective randomized studies proving a decrease of CRC-mortality in the range of 15-33% are available only for this type of programme. Screening of sporadic CRC was introduced on national basis in Federal Republic Germany in 1977 and in Czech Republic since the second half of the year 2000. With so many people dying of the disease, we cannot afford not to do its screening.

Colonoscopy↗

Contribution of HPLC mass screening for neuroblastoma to a decrease in mortality.

The aim of this study is the estimation of the contribution of HPLC mass screening for neuroblastoma to the decrease in deaths due to this disease. The mortality rates of malignant neoplasms of the adrenal glands (ICD 9, 1940; ICD 10, C74; virtually all the cases of these codes are neuroblastoma during childhood) at 1-4 years of age in cohorts born in 1979-1984, 1985-1988, and 1989-1992 in the whole of Japan were calculated, using data obtained from the Ministry of Health and Welfare. The numbers of infants screened by HPLC in the cohorts were estimated through the reports of the Ministry of Health and Welfare and the database of the Japanese Society for Mass-screening. The mortality of the cohort born in 1989-1992, in which 77.8% of the live births were screened by HPLC, was 1.73 per 100,000 live births. This is about half of that (3.26) of the cohort born in 1979-1984, in which few infants were screened. On the assumption that cases of the 1985-1988 and 1989-1992 cohorts died according to the mortality rate of the 1979-1984 cohort, the expected numbers of deaths were estimated; that for the 1985-1988 cohort was 178.51 (of them, that for the infants screened by HPLC was 39.65), and that for the 1989-1992 cohort was 159.78 (of them, that for the infants screened by HPLC was 124.33). The observed numbers of deaths were 145 and 85, respectively. Assuming that non-HPLC methods have no effects and using 2 unknown quantities x (contribution of HPLC) and y (other factors), simultaneous equations (1) 178.51 - 39.65x - 178.51y = 145 and (2) 159.78 - 124.33x - 159.78y = 85 were made. Solving them, x = 0.5041 and y = 0.0757 were obtained. In conclusion HPLC screening targeting infants aged 6 months reduces death of adrenal neuroblastomas at 1-4 years of age by about 50%.

Adrenal Gland Neoplasms↗

Considerations in using tumor markers: what the psycho-oncologist needs to know.

Tumor markers are measures of biological features of a cancer. By revealing important biological aspects of the tumor, tumor markers can be useful in staging patients, predicting cancer outcomes, and guiding treatments. The psychological consequences of using tumor markers are virtually unknown. In this review article, we draw on clinical studies involving the psychological impact of risk information, screening, prognostic information and surveillance of cancer. Such studies may be helpful in considering possible psychological reactions to tumor marker information in clinical practice.

Attitude to Health↗

Preliminary estimates of the virtually safe dose for tumors obtained from the maximum tolerated dose.

The purpose of this paper was to examine the correlation between the maximum tolerated dose (MTD) and the low-dose estimate of the virtually safe dose (VSD) for animal carcinogens. Chronic bioassay results from the National Cancer Institute/National Toxicology Program carcinogenesis screening program were used. Estimates of the VSD were obtained by linear low-dose extrapolation for which an adequate dose-response relationship existed at the same tumor site in the same sex for both rats and mice. Estimates of the VSD were compared with the MTD for 69 tumor sites from 38 chemicals for rats and mice. The MTDs ranged from high to low toxicity (1 ppb to 4.4% in the diet). The overall geometric mean of the ratio of the MTD to the VSD corresponding to a maximum estimated risk of 10(-6) was 3.8 x 10(5). Of the 138 cases, only 3 cases were more than a factor of 10 from the mean ratio. This suggested that a quick estimate of the VSD could be obtained by dividing the MTD, obtained from a subchronic study, by 400,000. Further, if the human exposure is less than 10(-7) X MTD, the estimated risk is likely to be negligible even if the chemical is a carcinogen. It may not be worthwhile to conduct a chronic bioassay for the purpose of demonstrating a negligible risk, if the chemical is likely to be carcinogenic, unless the human exposure is extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Virtual tools for teaching electrocardiographic rhythm analysis.

Electrocardiographic (ECG) rhythm analysis is inadequately taught in training programs, resulting in undertrained physicians reading a large percentage of the 40 million ECGs recorded annually. The effective use of simple tools (calipers, ruler, and magnifier) required for crucial measurements and comparisons of intervals requires considerable time for interactive instruction and is difficult to teach in the classroom. The ECGViewer (Blaufuss Medical Multimedia Laboratories, Palo Alto, Calif) program was developed using virtual tools easily manipulated by computer mouse that can be used to analyze archived scanned ECGs on computer screens and classroom projection. Trainees manipulate the on-screen tools from their seats by wireless mouse while the instructor makes corrections with a second mouse, in clear view of the trainees. An on-screen ladder diagram may be constructed by the trainee and critiqued by the instructor. The ECGViewer program has been successfully used and well received by trainees at medical school, residence, and subspecialty fellow level.

Arrhythmias, Cardiac↗

From famine to feast? Selecting nuclear DNA sequence loci for plant species-level phylogeny reconstruction.

Phylogenetic analyses of DNA sequences have prompted spectacular progress in assembling the Tree of Life. However, progress in constructing phylogenies among closely related species, at least for plants, has been less encouraging. We show that for plants, the rapid accumulation of DNA characters at higher taxonomic levels has not been matched by conventional sequence loci at the species level, leaving a lack of well-resolved gene trees that is hindering investigations of many fundamental questions in plant evolutionary biology. The most popular approach to address this problem has been to use low-copy nuclear genes as a source of DNA sequence data. However, this has had limited success because levels of variation among nuclear intron sequences across groups of closely related species are extremely variable and generally lower than conventionally used loci, and because no universally useful low-copy nuclear DNA sequence loci have been developed. This suggests that solutions will, for the most part, be lineage-specific, prompting a move away from 'universal' gene thinking for species-level phylogenetics. The benefits and limitations of alternative approaches to locate more variable nuclear loci are discussed and the potential of anonymous nongenic nuclear loci is highlighted. Given the virtually unlimited number of loci that can be generated using these new approaches, it is clear that effective screening will be critical for efficient selection of the most informative loci. Strategies for screening are outlined.

Cell Nucleus↗

In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe.

One of the most difficult challenges of oncology is to improve methods for early tumor detection, which is crucial for the success of cancer therapy and greatly improves the survival rate. Underglycosylated mucin-1 antigen (uMUC-1) is one of the early hallmarks of tumorigenesis and is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas as well as in nonepithelial cancer cell lines, as well as in hematological malignancies such as multiple myeloma, and some B-cell non-Hodgkin lymphomas. In this study, we designed, synthesized, and tested a novel multimodal imaging probe specifically recognizing in vivo uMUC-1 antigen in an animal model of human cancer. Furthermore, in vivo magnetic resonance- and near-infrared-imaging experiments on tumor-bearing animals showed specific accumulation of the probe in uMUC-1-positive tumors and virtually no signal in control tumors. We expect that this probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.

Amino Acid Sequence↗

Venous thromboembolism as first manifestation of cancer.

Since Trousseau's time numerous studies have addressed the relationship between cancer and venous thromboembolism (VTE) providing firm evidence of the increased risk of subsequent clinically overt malignancy during the follow-up of patients with idiopathic VTE. These malignancies are not limited to certain subtypes, but involve virtually all body systems. This knowledge has led to a long-standing debate on the need to screen for occult malignancies patients with idiopathic VTE with no clinical evidence of cancer at the time of the index thrombotic event. In fact the high incidence of newly discovered cancers does not automatically imply that screening is indicated in these patients since it is unknown whether a substantial proportion of cancers can be diagnosed, whether the diagnosed cancers are treatable and what the impact on cancer-related mortality is. Proper clinical trials are being conducted to find an answer to these questions.

Cohort Studies↗

Cystatin C as a marker for detection of early renal failure in diabetes type 2 patients.

UNLABELLED: The epidemiological studies have show dramatic increase and prevalence of end stage renal disease in patients with type 2 diabetes therefore early markers of diabetic nephropathy need to be identified (1). During the treatment of patients at the Clinic of endocrinology, diabetes mellitus and metabolic diseases in Sarajevo, we observed a necessity of application of new markers in assessment of early renal failure. Serum cystatin C level is another marker of renal function. Cystatin C is freely filtered at the level of the glomerulus and virtually all is re-absorbed and metabolized by the proximal tubular cells. Serum cystatin C is a screening test and an early indicator and predictor of the development of renal failure. AIM OF THE STUDY: To estimate correlation among cystatin C, serum creatinine and albuminuria in diabetes type 2 patients for assessment of early renal failure. Serum cystatin C as a screening test has to be considered in the treatment of diabetes type 2 patients for assessment of early renal failure.

Albuminuria↗

Classical galactosaemia in Chinese: A case report and review of disease incidence.

We report a case of galactose-1-phosphate uridyl transferase (GALT) deficiency in a full-term Chinese neonate, who presented with atypical biochemical features of hyperammonaemia in addition to the classical presenting features of jaundice and lethargy after feeding. Red cell GALT activity was virtually absent in the patient while 50% of normal activity was found in parents and a sibling. Mutation screening excluded both Q188R and N314D as the causative mutation in GALT gene, which suggested a possible genetic segregation among ethnic groups. Data from a Taiwan screening program suggested that the incidence of the disease was approximately 1 in 400 000 in the Chinese population which was a sixth of that in Caucasian populations.

Ammonia↗

[Determination of complement in an automatic mode].

A method for the complement determination is suggested by a 50 percent hemolysis microtest with the use of ELISA processor II for automated procedure and registration. The results obtained with this technique virtually do not differ from the data of the routine macromethod. The method is suggested for mass immunologic screenings.

Complement System Proteins↗

[The effect of alcohol abuse on the health status of women and their children].

A total of 250 women, working in the same enterprise in similar conditions, with similar communal conditions were examined. The data of questionnaires and case histories evidence that 5% of women virtually never used alcohol, 85% of women used alcohol in reasonable amounts, 10% of women abused alcohol. The screening methods that were effective in examinations of men suffering from chronic alcoholism were found useless in a population of working women. That is why adequate screening methods are to be developed for the assessment of the involvement of female organs and systems. The onset of menarche is delayed in women who abuse alcohol in the period of the menstrual function development. The findings of this research are in line with the previously published data on disorders of the reproductive function in women abusing alcohol and of fetal development in case of an antenatal exposure to ethanol.

Adolescent↗

Experience with V-STORE: considerations on presence in virtual environments for effective neuropsychological rehabilitation of executive functions.

The paper discusses the use of immersive virtual reality systems for the cognitive rehabilitation of dysexecutive syndrome, usually caused by prefrontal brain injuries. With respect to classical P&P and flat-screen computer rehabilitative tools, IVR systems might prove capable of evoking a more intense and compelling sense of presence, thanks to the highly naturalistic subject-environment interaction allowed. Within a constructivist framework applied to holistic rehabilitation, we suggest that this difference might enhance the ecological validity of cognitive training, partly overcoming the implicit limits of a lab setting, which seem to affect non-immersive procedures especially when applied to dysexecutive symptoms. We tested presence in a pilot study applied to a new VR-based rehabilitation tool for executive functions, V-Store; it allows patients to explore a virtual environment where they solve six series of tasks, ordered for complexity and designed to stimulate executive functions, programming, categorical abstraction, short-term memory and attention. We compared sense of presence experienced by unskilled normal subjects, randomly assigned to immersive or non-immersive (flat screen) sessions of V-Store, through four different indexes: self-report questionnaire, psychophysiological (GSR, skin conductance), neuropsychological (incidental recall memory test related to auditory information coming from the "real" environment) and count of breaks in presence (BIPs). Preliminary results show in the immersive group a significantly higher GSR response during tasks; neuropsychological data (fewer recalled elements from "reality") and less BIPs only show a congruent but yet non-significant advantage for the immersive condition; no differences were evident from the self-report questionnaire. A larger experimental group is currently under examination to evaluate significance of these data, which also might prove interesting with respect to the question of objective-subjective measures of presence.

Cognition Disorders↗

Measurement of crosslinked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis.

Levels of plasma crosslinked fibrin derivatives, a sensitive and direct marker of the lysis of intravascular crosslinked fibrin, were measured serially in 135 patients undergoing major abdominal surgery to determine their behavior and their use as a screening test for postoperative venous thrombosis. Preoperative levels and levels on the first postoperative day were significantly higher by both enzyme immunoassay and latex assay in 31 patients who developed venous thrombosis (positive venography) than in 104 patients who did not (negative 125I fibrinogen leg scan). Preoperative XLFDP levels 400 ng/ml (enzyme immunoassay) had a sensitivity to the diagnosis of postoperative venous thrombosis of 58%, specificity 74%, positive predictive value 41% and negative predictive value of 85%. The sensitivity of XLFDP levels over 1200 ng/ml on the first postoperative day was 65%, specificity 73%, positive predictive value 38% and negative predictive value 89%. These cutoff values were chosen (high negative predictive value) to allow identification of patients who were unlikely to have venous thrombosis. Measurement of plasma XLFDP, a simple inexpensive test, could be used as a screen to select patients for surveillance procedures (IPG or duplex ultrasonography). A substantial increase in XLFDP levels (greater than 500 ng/ml) occurred in virtually all patients, suggesting that fibrinolysis is not 'shutdown' postoperatively and that these assays reflect lytic activity at the fibrin surface more accurately than do measurements of plasminogen activators and their inhibitors.

Abdomen↗