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PubMed2001

Diagnosis of Helicobacter pylori infection: noninvasive methods compared to invasive methods and evaluation of two new tests.

OBJECTIVES: Current guidelines recommending Helicobacter pylori eradication treatment without performing endoscopy in certain patients highlight the importance of noninvasive tests. Our aim was to determine the accuracy of two new tests: the antigen stool test and Helicoblot 2.1 (an immunoblot used on serum) as well as the 13C urea breath test and ELISA serology in comparison to invasive tests for the pretreatment diagnosis of H. pylori infection. METHODS: Helicobacter pylori infection was diagnosed prospectively in 104 untreated patients using eight different tests. Invasive tests included culture, urease test (CLOtest), histology, and PCR; noninvasive tests included the 13C urea breath test, IgG serology (Pyloriset EIA-G), immunoblot (Helicoblot 2.1), and antigen stool detection (Premier Platinum HpSA). A predefined gold standard based on biopsy tests was used to define H. pylori status, as well as an empirical approach. RESULTS: There was no statistically significant difference between the different tests. The sensitivity of the noninvasive tests ranged between 88.9% and 95.6% (stool test: 88.9%, 95% CI: 82.7-95.1, and Helicoblot 2.1: 95.6%, 95% CI: 91.5-99.6) and the specificity ranged between 92.6 and 98.1% (stool test: 94.4%, 95% CI: 84.6-98.8, and Helicoblot 2.1: 92.6%, 95% CI: 91.5-96.2) when a predefined gold standard was used. CONCLUSIONS: Most tests had sensitivities, specificities, and predictive values >90%. The noninvasive tests are accurate for the diagnosis of H. pylori infection. Helicoblot 2.1 performed as well as the best ELISA kit. The HpSA is a promising direct noninvasive test that can be applied easily to evaluate H. pylori status.

Breath Tests↗
PubMed2004

Dietary fructose and gastrointestinal symptoms: a review.

It has been proposed that fructose may cause or aggravate symptoms in patients with functional gastrointestinal disorders. Fructose is commonly used to sweeten processed foods, and the prevalence of incomplete fructose absorption (25 g, 10%) in healthy subjects is as high as 50%. The only controlled study that has been performed did not demonstrate a higher prevalence of fructose-induced gastrointestinal symptoms or incomplete fructose absorption in patients with functional gastrointestinal disorders. The amount and concentration of fructose used to evaluate absorption by breath testing has varied among studies. Moreover, dietary sources of fructose usually contain glucose, which increases fructose absorption in healthy subjects. Thus, breath testing with fructose alone may not reflect fructose ingestion under normal circumstances. Given these limitations, we suggest that a practical, empirical approach to testing in patients with suspected incomplete fructose absorption is to restrict fructose ingestion. Additional controlled studies are needed to clarify the relation between incomplete fructose absorption and symptoms, assess the effects of co-ingestion of other sugars on fructose absorption, and evaluate the effects of eliminating sugars from the diet on gastrointestinal symptoms.

Diet↗
PubMed1989

Psychodynamic features in borderline personality disorder identified by a subliminal test, the Defense Mechanism Test.

Twenty-seven psychiatric inpatients, diagnosed according to DSM-III and the Diagnostic Interview for Borderline (DIB), and 7 healthy controls were tested with the Defense Mechanism Test (DMT), a test of subliminal perception based on psychoanalytic theory. In the test a specific stimulus is presented subliminally in a tachistoscope and the patient's perceptual distortions are registered. Patients with borderline personality disorder (BPD) were compared with patients with other personality disorders, patients with schizophrenic disorders and healthy controls. Specific perceptual distortions were identified among patients with BPD. Some individual DMT signs correlated with some deviant behaviors as identified by the DIB. The findings supported the psychodynamic validity of the concept of borderline personality disorder. It is concluded that DMT is a promising research instrument that provides an empirical approach to crucial psychodynamic phenomena.

Adult↗
PubMed2001

Demographers and the study of mortality: scope, perspectives, and theory.

Demographers have for a long time adopted an empirical approach to the study of the levels and trends of mortality, fertility, and population size. They depend for their analyses on data, usually collected until recent times by government and often for other purposes. Modern demography had its origins in Britain in the second half of the seventeenth century. The major focus of demographers has usually been on mortality, although fertility studies predominated in the 1960s and 1970s. Mortality decline in the West only became certain in the late nineteenth century. Until the 1960s the fastest mortality declines were for the young, but an unheralded mortality decline among the old thereafter became important. The world, especially in economically advanced countries, is faced with an increasingly high proportion of old people, explained largely, not by mortality decline, but by fertility decline. Explanations for the mortality transition place different emphases on the role of modern medicine, better nutrition, and behavioral and social change, particularly rising levels of education. Even among the old, at least until 85 years of age, there are wide differentials in mortality by educational level. Analysts have divided the mortality transition into stages: (1) high, pretransitional mortality, (2) early transitional mortality with the decline explained by the conquest of infectious disease, and (3) late transitional mortality largely attributable to degenerative disease. Some have now added stage (4), the reduction or delay in death from degenerative causes. Attempts have been made to effect the convergence of demographic and epidemiological approaches to the analysis of mortality, and they have been more successful in the case of medical demographic than in social demographic approaches.

Adult↗
PubMed2006

Tissue distribution and metabolism of the tyrosine kinase inhibitor ZD6474 (Zactima) in tumor-bearing nude mice following oral dosing.

ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-quinazolin-4-amine; Zactima] is a tyrosine kinase inhibitor with antiangiogenic and antitumor activity currently undergoing human trials for cancer treatment. Pharmacokinetic studies in animal models are an important component in the clinical development of this agent to relate preclinical studies to patient treatment. In the studies presented here, the pharmacokinetics of ZD6474 was determined in plasma and tissues of MCF-7 tumor-bearing nude mice following single p.o. doses at 10, 25, and 50 mg/kg. Plasma area under the curve and Cmax were linear, increasing proportionally with dose. Tissue analysis showed that ZD6474 is extensively distributed to tissues, with liver and lung accumulating concentrations of 212 microg/g (approximately 450 microM) and 161 microg/g (approximately 340 microM), respectively. Tumor levels ranged from 27 to 71 microg/g at Cmax levels across the three dose ranges, and ZD6474 was distributed to all of the tissues in a dose-dependent manner. Analysis of putative ZD6474 metabolites in feces found four, with the N-demethyl-piperidinyl-ZD6474 metabolite being the most prominent but still accounting for less than 2% of the total amount of ZD6474 present. The lack of significant metabolism of ZD6474 is consistent with the relatively long half-life in mice (approximately 30 h), as well as that seen in humans (approximately 120 h), and the primary method of drug elimination appears to be unchanged in the feces (approximately 25%). The incorporation of an empirical approach to dosing in mouse models of cancer in preclinical studies may allow for better prediction of clinical efficacy for ZD6474 alone and in combination with other therapeutic modalities based on equivalent drug exposure.

Angiogenesis Inhibitors↗
PubMed1990

Resource allocation: a plea for a touch of realism.

The problem of resource allocation in health has stimulated much thought and research, in attempts to provide objective, rational methods by which necessary choices can be made. One such method was proposed in a paper in this journal. The authors argued for a utilitarian approach, which they claimed to demonstrate was acceptable to society at large. This paper argues that the evidence supporting such a claim was flawed; such a utilitarian approach is not socially acceptable, and is therefore not relevant. Rather more relevant directions for research are discussed, based on the assertion that a degree of realism is essential when considering the problems of resource allocation.

England↗
PubMed2001

Is current practice around late termination of pregnancy eugenic and discriminatory? Maternal interests and abortion.

The attitudes of Australian practitioners working in clinical genetics and obstetrical ultrasound were surveyed on whether termination of pregnancy (TOP) should be available for conditions ranging from mild to severe fetal abnormality and for non-medical reasons. These were compared for terminations at 13 weeks and 24 weeks. It was found that some practitioners would not facilitate TOP at 24 weeks even for lethal or major abnormalities, fewer practitioners support TOP at 24 weeks compared with 13 weeks for any condition, and the difference in attitudes to TOP between 13 weeks and 24 weeks is most marked for pregnancies which are normal or involve a mild disorder. It is argued that a fetal abnormality criterion for late TOP is inconsistently applied, discriminatory and eugenic. Four possible moral justifications for current practice are examined, each of which would require significant changes to current practice. I argue in favour of a maternal interests criterion for any TOP.

Abortion, Eugenic↗
PubMed2002

Undignifying institutions.

Declarations of the importance of dignity in health care are commonplace in codes of practice and other mission statements, yet these documents never clarify dignity's meaning. Their vague aspirations are compared to comments from staff and patients about opportunities for and barriers against the promotion of dignity in elderly care institutions. These suggest that while nurses and health care assistants have an intuitive understanding of dignity, they either do not or cannot always bring it about in practice. Thus, despite stated intentions to promote dignity, it appears that the circumstances of at least some elderly care institutions cause patients to experience avoidable indignities. Such institutions are "undignifying institutions" because they fail to acknowledge dignity's basic components, focus excessively on quantifiable priorities, and have insufficient resources available to assure consistently dignifying care. As a partial solution, we argue that health workers should be taught to understand and specify the components of dignity, which will better prepare them to challenge undignifying practices and to recognise opportunities for dignity promotion.

Aged↗
PubMed2005

Investigating time patterns of variation in radiation cancer associations.

AIMS: In occupational settings, carcinogenic exposures are often repeated or protracted over time. The time pattern of exposure accrual may influence subsequent temporal patterns of cancer risk. The authors present several simple models that may be used to evaluate the influence of time since exposure or age at exposure on cancer incidence or mortality in an occupational cohort. METHODS: A cohort of 40,415 nuclear industry workers was identified via the Canadian National Dose Registry. Vital status and cause of death were ascertained through 1994. Associations between ionising radiation and mortality due to lung cancer, leukaemia, and cancers other than lung and leukaemia were quantified using conditional logistic regression models with risk sets constructed by incidence density sampling. A step function, a bilinear function, and a sigmoid function were used to evaluate temporal variation in exposure effects. RESULTS: Step and sigmoid functions were used to explore latency and morbidity periods. For analyses of lung cancer, leukaemia, and other cancers the best fitting models were obtained when exposure assignment was lagged by 13, 0, and 5 years, respectively. A bilinear function was used to evaluate whether exposure effects diminished with time since exposure. In analyses of lung cancer and leukaemia, there was evidence that radiation effects attenuated with protracted time since exposure. In analyses of age at exposure, there was evidence of variation in radiation mortality associations for analyses of lung cancer and leukaemia; discounting radiation doses accrued at younger ages (for example, 15-35 years) led to significant improvements in model fit. CONCLUSIONS: This paper illustrates empirical approaches to evaluating temporal variation in the effect of a protracted exposure on disease risk.

Adolescent↗
PubMed1983

Empirical strategy for analytical fractionation of epithelial cells.

Despite the importance of cell fractionation methods in studies of epithelial transport mechanisms and of a variety of subcellular processes, current practices in cell fractionation have a number of shortcomings. Most cell fractionation studies depend on biochemical markers, but they provide little independent confirmation of the initial assumptions that markers are uniquely associated with particular subcellular structures and that they are uniformly distributed over the surfaces with which they are associated. Moreover, it is generally difficult and time-consuming to design new membrane isolation procedures. After reviewing the analytical nature of physical separation procedures, I suggest an empirical approach to cell fractionation that is both general and comprehensive. This approach uses physical separation procedures to generate spatial distributions of particles in which position is related to such physical properties as sedimentation coefficient, density, cholesterol content, surface charge, and coefficient of partitioning in aqueous polymer two-phase systems. Determination of the frequency distributions of biochemical markers permits detection of separate populations of particles even when the populations lack unique markers. This process requires no a priori assumptions about the subcellular localizations of particles.

Alkaline Phosphatase↗
PubMed1987

Reflectance measurements of hematocrit and oxyhemoglobin saturation.

Fiberoptic oximeters measure oxyhemoglobin saturation from the optical reflectance of whole blood, but the calibration of such oximeters is hematocrit dependent. Therefore, using photon-diffusion theory and an empirical approach, we have developed a new reflectance method that determines hematocrit and correspondingly corrects the oxyhemoglobin-saturation measurement. Our method employs four fiber-optic light guides, a photodetector, and three inexpensive light-emitting diodes (one with emissions at 660 nm and two at 813 nm). Hematocrit is determined from the ratio of reflectances from the differently spaced emitting fibers at 813 nm and is used to correct the 813-660 nm measurement of oxyhemoglobin saturation. In red cell suspensions, the mean difference between reflectance measurements of hematocrit and conventional determinations was only 2.09% (r = 0.99), and when compared with conventional gasometric measurements of oxyhemoglobin saturation, the reflectance method yielded the same calibration curve for different hematocrits and gave a mean difference of only 2.67%. Although the technique is demonstrated with a cuvette appropriate for an extracorporeal circulation in animal experiments, it could possibly be further developed for fiber-optic catheter oximeters.

Animals↗
PubMed1985

A theory of diffuse light scattering by lungs.

We present a theoretical treatment of backscattered light from the interior of a lung illuminated by a thin beam of light normally incident on the pleural surface. An approximate formula is developed describing how the backscattered intensity varies with distance from the point of light entry. This is shown to depend markedly on the optical mean free path and on the effective extinction coefficient. We attempt to relate the optical mean free path to the mean alveolar size. This relationship is found to depend primarily on septal reflection and refraction. Reflection is treated quantitatively. Refraction is much more difficult and may have to be approached empirically. We present here the rudiments of a technique with implications for the possibility of dynamic stereology.

Light↗
PubMed2003

Role of feedforward control of movement stability in reducing slip-related balance loss and falls among older adults.

Human upright posture is inherently unstable. To counter the mechanical effect of a large-scale perturbation such as a slip, the CNS can make adaptive adjustments in advance to improve the stability of the body center-of-mass (COM) state (i.e., its velocity and position). Such feedforward control relies on an accurate internal representation of stability limits, which must be a function of anatomical, physiological, and environmental constraints and thus should be computationally deducible based on physical laws of motion. We combined an empirical approach with mathematical modeling to verify the hypothesis that an adaptive improvement in feedforward control of COM stability correlated with a subsequent reduction in balance loss. Forty-one older adults experienced a slip during a sit-to-stand task in a block of slip trials, followed by a block of nonslip trials and a re-slip trial. Their feedforward control of COM stability was quantified as the shortest distance between its state measured at seat-off (slip onset) and the mathematically predicted feasible stability region boundary. With adaptation to repeated slips, older adults were able to exponentially reduce their incidence of falls and backward balance loss, attributable significantly to their improvement in feedforward control of stability. With exposure to slip and nonslip conditions, subjects began to select "optimal" movements that improved stability under both conditions, reducing the reliance on prior knowledge of forthcoming perturbations. These results can be fully accounted for when we assume that an internal representation of the COM stability limits guides the adaptive improvements in the feedforward control of stability.

Adaptation, Physiological↗
PubMed2000

Improved patient outcomes with BCG immunotherapy vs. chemotherapy - Swedish and worldwide experience.

Intravesical therapy of superficial bladder cancer has been in routine use since the introduction of thiotepa in 1961. An empirical approach has been used to optimize this kind of treatment - clinical data are, unfortunately, often lacking. Marker lesion studies indicate that BCG is more effective than cytostatic drugs. For the prophylaxis of recurring disease, the recurrence rate is lower with chemotherapy than in controls, but no effect on the risk of progression has been verified. None of the chemotherapy drugs used has proved superior to the others. Randomized trials have recently been performed with mitomycin C vs. BCG. Comparison of the different trials is difficult due to the use of different methodologies. The majority of the studies found BCG to be more effective in lowering the number of recurrences, but progression rates were not significantly different. Trials with combinations of BCG-mitomycin C or epirubicin-interferon have yielded promising results.

Administration, Intravesical↗
PubMed1994

Empiricism versus science in the teaching of nephrology.

Recent changes in medical courses in Italy reflect a recognition that both theoretical education and clinical practice are essential components of a doctor's training. These two parallel branches of medical education find their origins in the beliefs of Galen, mentor of medicine as a pure science, and of Alexander of Aphrodisias, promoter of the predominant role of empiricism. Neither a dogmatic nor an empiric approach to the study of medicine, however, is sufficient on its own.

Education, Medical↗
PubMed1996

Treatment of hepatic encephalopathy in patients with cirrhosis of the liver.

The treatment of hepatic encephalopathy is predominantly an empirical approach because the process pathogenesis of this syndrome is uncertain. Many treatment trials have been published, but few fulfill the usually accepted criteria for optimum study design. Lack of placebo controls, inadequate sample size and the difficulty in assessing the severity of encephalopathy are noteworthy examples. Treatments based on reducing ammoniagenic factors in the intestinal tract and promoting urinary waste nitrogen elimination are discussed. Other forms of therapy based on the false neurotransmitter and gamma-aminobutyric hypotheses are reviewed before outlining a practical approach to treatment of hepatic encephalopathy in clinical practice.

Amino Acids, Branched-Chain↗
PubMed1990

Urinary incontinence in old age: helping the general practitioner to make a diagnosis.

Since urinary incontinence is one of the major presenting symptoms of illness in old age, all those who deal with this professionally should have a clear plan in mind as to how to proceed with diagnosis and management. Such a plan is outlined here based first of all on history and examination and easily performed tests and followed, if the problem still remains, by an empirical approach based on the major presenting symptom--urge incontinence, stress incontinence or incontinence of which the patient is unaware.

Aged↗