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PubMed2005

Switching of prescription drugs to over-the-counter status: is it a good thing for the elderly?

Prescription medicines are increasingly being switched to over-the-counter (OTC, nonprescription) status in the developed world, with the support of government policy. These changes may provide greater choice for individuals and offer potential savings in government spending on health while expanding the market for pharmaceutical companies. However, there is concern regarding the safety of these reclassifications. Elderly people are the largest consumers of prescription and OTC medicines and are more vulnerable to drug adverse effects and the risks of multiple or inappropriate medications. Commonly purchased agents such as NSAIDs have recognised adverse effects which have been shown to be more common in the elderly. Furthermore, all sedatives, including antihistamines, have a propensity to cause falls in older people. As many doctors do not ask patients about OTC medicine use, problems related to use of these drugs may go undetected. Furthermore, the increased availability of OTCs may result in a delay in patients consulting medical practitioners for potentially serious conditions, although this has not so far been investigated. In the UK, the recent switch of a low-dose HMG-CoA reductase inhibitor (statin) to OTC status has caused concern. Although there might theoretically be some benefits from improved access to medications used in primary and secondary prevention of heart disease, the actual outcomes of use of this reduced dose of the statin will be difficult or impossible for patients or practitioners to monitor. OTC drug use implies a mutual responsibility for communication between patients and health professionals that in practice is not always achieved. Epidemiological research is needed to investigate patterns of OTC use and evaluate the potential risks of OTC medicines in elderly people. Governments, regulatory bodies, professionals and the drug industry have a responsibility to ensure that robust systems are in place if the increased use of OTC medicines by elderly people is to be safe and effective.

Aged↗
PubMed2000

A neural network based virtual high throughput screening test for the prediction of CNS activity.

A virtual high throughput screening test to identify potentially CNS-active drugs has been developed. Discrimination was based on the knowledge available in databases containing CNS-active (Cipsline from Prous Science) and inactive compounds (Chemical Directory from Sigma-Aldrich). Molecular structures were represented using 2D Unit y fingerprints and a feedforward neural network was trained to classify molecules regarding their CNS activity. The parameterized network was validated by reclassification of the training set elements, by the classification of a test set preselected from the Prous database, and also by the prediction of activity for known CNS drugs not used in the training set but available in the Medchem database (Daylight). These tests revealed that our neural net recognized at least 89% of CNS-active compounds and would be suitable for use in our virtual screening protocol.

Artificial Intelligence↗
PubMed1991

Color Doppler sonography in the evaluation of erectile dysfunction: patterns of temporal response to papaverine.

Most studies of duplex Doppler sonography for the assessment of erectile dysfunction involve determination of peak systolic velocities 5 min after intracavernosal injection of papaverine. The purpose of this study was to determine the effect of the timing of Doppler measurements of flow after papaverine injection for establishing the presence of arterial and venous abnormalities. Color Doppler sonography was performed in 75 patients for evaluation of vasculogenic impotence. After intracavernosal injection of 60 mg of papaverine, measurements of peak systolic and end-diastolic velocities were obtained in each cavernosal artery at 5-min intervals for a total of 30 min. A peak systolic velocity of less than 25 cm/sec was used as the threshold for arterial insufficiency. An end-diastolic velocity of greater than 5 cm/sec was used to predict venous incompetence. Scanning was performed for direct assessment of dorsal venous flow. Thirty patients were subsequently evaluated by cavernosometry and cavernosography. In most patients (76%), maximum response to papaverine was achieved within the first 5 min. In eight patients, significant increases in systolic velocity were seen only after 5 min. In 10 patients, significant changes in end-diastolic velocity between 5 and 30 min resulted in diagnostic reclassification. Data acquisition for 30 min significantly improved the sensitivity (95%) and specificity (83%) for the prediction of venous incompetence in patients with correlative cavernosography. Transient, early dorsal vein flow was noted in normal subjects. Persistent dorsal vein flow had an 80% sensitivity and 100% specificity for venous incompetence. Our results suggest that, when using color Doppler sonography, gathering data for 30 min may improve the prediction of vasculogenic impotence.

Adult↗
PubMed1999

Leifsonia gen. nov., a genus for 2,4-diaminobutyric acid-containing actinomycetes to accommodate "Corynebacterium aquaticum" Leifson 1962 and Clavibacter xyli subsp. cynodontis Davis et al. 1984.

"Corynebacterium aquaticum" was first proposed by Leifson in 1962 but not included in the approved lists of bacterial names in 1980. This species has been left from reclassification of the genus Corynebacterium because of the unusual chemotaxonomic characteristics such as 2,4-diaminobutyric acid (DAB) in the peptidoglycan and menaquinones of MK-10 and MK-11. A close relationship of "C. aquaticum" to the genera Agromyces and Rathayibacter has been pointed out from the viewpoint of chemotaxonomic profiles and phylogeny based on the 16S rDNA sequences. An analysis of DAB isomers of the peptidoglycan distinguished "C. aquaticum" clearly from these genera by possessing both L-DAB and D-DAB. We also found that the type strain of Clavibacter xyli subsp. cynodontis and two strains of amine-decomposing bacteria showed the similar chemotaxonomic features and formed a cluster with "C. aquaticum" in the phylogenetic tree based on 16S rDNA sequences in the family Microbacteriaceae. Considering these results, we propose a new genus Leifsonia to accommodate the four strains. The four species, Leifsonia aquatica sp. nov., nom. rev., comb. nov. (type species, type strain=JCM 1368), Leifsonia shinshuensis sp. nov. (type strain=DB102=JCM 10591), Leifsonia naganoensis sp. nov. (type strain=DB103=JCM 10592), and Leifsonia cynodontis comb. nov. (type strain=JCM 9733=ICMP 8790), were proposed here for the strains.

Journal Article↗
PubMed2006

Development of a collagen-binding activity assay as a screening test for type II von Willebrand disease in dogs.

OBJECTIVE: To develop an assay to measure canine von Willebrand factor (vWF):collagen-binding activity (CBA) to screen for type 2 von Willebrand disease (vWD) in dogs. SAMPLE POPULATION: 293 plasma samples submitted for analysis of canine vWF antigen (vWF:Ag) and 12 control plasma samples from dogs with inherited type 2 or 3 vWD. PROCEDURE: Bovine collagens were evaluated for suitability as binding substrate for vWF. Assay sensitivity to depletion, proteolytic degradation, or a genetic deficiency of high-molecular-weight vWF were determined. Amounts of vWF:Ag and vWF:CBA were measured. The ratio of vWF:Ag to vWF:CBA was used to discriminate between type 1 and type 2 vWD. RESULTS: An assay for canine vWF activity was developed by use of mixed collagen (types I and III). When vWF:Ag was used to subtype vWD, 48% of the dogs were classified as clinically normal, 9% as indeterminate, and 43% as type 1 vWD. Inclusion of vWF activity resulted in reclassification of 5% of those identified as type 1 to type 2 vWD. However, vWF:CBA of the reclassified dogs was not persistently abnormal, a finding compatible with acquired type 2 vWD. Some Doberman Pinschers had lower antigen-to-activity ratios than other breeds with type 1 vWD, suggesting that Doberman Pinschers have more functional circulating vWF. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of canine vWF activity should be included among the vWF-specific assays used to confirm type 2 vWD. The prevalence of inherited forms of type 2 vWD in screened dogs is lower than acquired forms that can result secondary to underlying disease.

Animals↗
PubMed1997

The "jump" and "release" effects: some observations on the perception of causality.

Two experiments studied the "release" and "jump" effects. Suppose that--on a homogeneous background--a single object moving on a straight trajectory has a constant physical velocity along all its path except in the middle where this velocity is higher or lower for a short time. The release effect occurs when this velocity is lower and the jump effect when it is higher. In the release effect, the object appears to be released from something that held it back. In the jump effect, the object appears to make a jump forward. In line with Premack's 1990 view, these effects suggest a reclassification of causal phenomena in terms of the perceived origin of the change in movement. This origin is perceived as external in Michotte's launching effect and as both internal and external in the release effect and as internal in the jump effect.

Color Perception↗
PubMed2002

The introduction of an occupational health management system for solving issues in occupational health activities in Japan.

An important challenge to occupational health services in Japan is the necessary shift from regulation-based occupational health program to health risk-based program. The Occupational Safety and Health Management System (OSHMS) is an effective tool for introducing risk-based activities. To date, the Five Management system has been used to manage occupational health activities. This classification, however, does not show the interactions among the listed activities. Nor is it clear how this system contributes to the PDCA (Plan/Do/Check/Act) cycle for continual improvement. The category in the Five Management system called "Roles of the Occupational Physician" covers most of the occupational health services required in Japan. The items listed in the Five Management system were compared to the guidelines of OSHMS from the International Labour Office and issues that should be solved for occupational health activities with OSHMS were clarified. Seven issues are discussed in this paper; (1) occupational safety and health policy and audit that can drive the PDCA cycle effectively, (2) reclassification of occupational health activities with several different objectives, (3) set up of targets, (4) risk assessment methods that can prioritize health risks compared to safety risks, (5) exposure assessment methods for risk assessment, (6) flexibility of laws and regulations, and (7) development of talented professionals for risk-based occupational health activities.

Health Policy↗
PubMed1975

Diagnosis of liver diseases by laboratory results and discriminant analysis. Identification of best combinations of laboratory tests.

Patients with different liver diseases were studied by discriminant analysis. Groups of patients classified mainly on the basis of liver biopsy findings showed functional differences which permitted a consistent reclassification by discriminant functions using laboratory results. Optimal combinations of laboratory tests for the separation of liver diseases were defined. Different combinations were found, dependent on the subsets of liver diseases studied.

Acute Disease↗
PubMed1980

Pancreatic iso-amylase in serum as a diagnostic test in different clinical situations. A simulation study.

The potential use of a pancreatic iso-amylase test has been studied by computer simulation. This simulation was performed to assess the quality requirements on the test in different clinical situations. It was shown that, in most situations studied, an optimal discriminating level and an optimal analytical quality (imprecision and bias) could be established. In one situation studied in more detail, it was found that the influence of pre-analytical variation, duplicate determinations, reclassification of borderline cases and size of reference sample groups were of minor importance. The weighting ratio of false negatives: false positives was found to be critical for the results. It is concluded that a simulation study of this type can be recommended prior to entering the phases of analytical refinement and clinical testing on patients.

Adult↗
PubMed1981

Free thyroxine, thyroxine/TBG ratio and other in vitro tests of thyroid function evaluated by discriminant analysis.

T4, T3, TSH, FT4 (Corning method), TBG, T3U and a diversity of free thyroid hormone indices were determined in serum from 72 reference persons and 337 patients with either thyroid diseases, TBG abnormalities, non-thyroid illnesses, or medications known to affect the results of thyroid function tests. Ninety-six per cent were 20 years or older. None of the laboratory parameters showed significant age or sex dependence, whereas systemic illness and medications frequently influenced test results. Thus the mean values of all patient groups differed significantly from those of the reference group in two or more laboratory tests, and significantly from those of the reference group in two or more laboratory tests, and significant differences were detected in 73% of the total number of 209 paired comparisons of test results between reference and patient groups. As a single parameter, free thyroxine index was found to be a marginally more efficient thyroid function discriminator than FT4, which again was more efficient than the T4/TBG ratio. However, non of these parameters were included in the combinations of laboratory tests identified as optimum by discriminant analysis. The overall optimum test combination was T4, TSH and T3U, which had an efficiency for correct thyroid function reclassification better than 98% in the total material. T3 replaced TSH in distinguishing between hyperthyroidism and euthyroidism.

Adolescent↗
PubMed1997

An improved rapid troponin T test with a decreased detection limit: a multicentre study of the analytical and clinical performance in suspected myocardial damage.

In a multicentre study, we evaluated the analytical and diagnostic performance of the second version of the TROPT rapid test (TROPT 2, CARDIACT in the US). We tested TROPT 2 on 796 blood samples from 487 patients admitted on suspicion of myocardial infarction between 1 and 72 h after onset of symptoms and determined cTnT ELISA and CK MB mass in the corresponding serum samples. Frequency distributions of the results with TROPT 2 showed a detection limit of 0.18 microgram/l (for 50% positive results) as determined by the quantitative cTnT ELISA method. In a total of 796 samples the sensitivities in the detection of myocardial infarction (WHO criteria) 8-12 h after onset of symptoms were highest for cTnT ELISA (98%), followed by the rapid assay and CK MB mass (92%). A subgroup of 87 patients was primarily classified by the WHO criteria for definite infarction. Based on the maximum values within each patient time-series, diagnostic sensitivities for infarction were 100% for TROPT2, cTnT ELISA and CK MB mass. The corresponding specificities were 90%, 82% and 100%, respectively. After reclassification summarizing all cases of myocardial damage (acute and subacute myocardial infarctions and minor myocardial damage) the sensitivities were 87% (TROPT2), 100% (cTnT ELISA) and 71% (CK MB mass). The specificities of all three markers were 100%. Over 50% of all cases of minor myocardial damage were detected by TROPT 2. The clinical evaluation showed that the diagnostic performance of TROPT 2 is only slightly lower than that of cTnT ELISA.

Angina, Unstable↗
PubMed1982

Sclerosing cholangitis in ulcerative colitis. A follow-up study.

In the 5-year period 1974-78, 48 (14%) of 336 patients with ulcerative colitis were found to have hepatobiliary disease. Endoscopic retrograde cholangiography (ERC) was successfully performed in 39 of these 48 patients, and sclerosing cholangitis was demonstrated in 19. One is excluded from this series because Crohn's disease was diagnosed at reclassification of the bowel disease. Two of the 18 patients with ulcerative colitis and sclerosing cholangitis have died, one of cholangiocarcinoma and one of an unrelated cause. The remaining 16 patients have been observed for a median period of 6 years (3-13 years) since the diagnosis of hepatobiliary disease. Ten have remained symptom-free, four have had intermittent or non-progressive symptoms, and two have developed symptoms of advanced chronic liver disease. The bilirubin level, which was initially raised in one of the patients, was elevated in four at the follow-up examination. Otherwise the laboratory values have remained stationary. Evidence of a progression of the hepatobiliary disease was found in most patients by repeated liver biopsy and particularly ERC. It is concluded that sclerosing cholangitis may remain asymptomatic for several years. Since progressive cholangiographic changes were often seen without concomitant worsening of symptoms, laboratory data, and liver biopsy findings, it is concluded that these criteria are of limited use in evaluating the progression of this disease.

Adult↗
PubMed1987

Transferability of a computer system for medical history taking and decision support in dyspepsia. A comparison of indicants for peptic ulcer disease.

The transferability of a British data base for differential diagnosis of dyspepsia using data obtained by computer interrogation was tested in 467 Swedish patients. The diagnostic value for peptic ulcer disease of symptoms such as frequent night pain relieved by food or antacids, smoking, family history of ulcer, food relief pain, male sex, and episodic pain was shown to be reproducible. However, for a number of symptoms their value for the diagnosis of peptic ulcer disease could not be reproduced in Swedish patients. The combined value of indicants was tested using a computer based algorithm for calculating diagnostic probabilities. The performance of this algorithm was poor when British data were applied to Swedish patients but reclassification of the Swedish patients on their own data base showed promising results. Crean and colleagues in Glasgow have developed a computer system for automated interrogation of patients with dyspepsia. The system utilises a large number of questions to obtain information regarding a maximum of 160 diagnostic indicants. The symptoms elicited from a patient can be compared with those of a large number of previously examined patients and the probabilities of ten different diagnoses can be calculated. The calculation of diagnostic probabilities is based on scores reflecting the diagnostic value of different symptoms in different diseases. After careful translation of questions the system has been transferred for use in Sweden. The present report is based on data from patients seen during the first two years with the system at a Swedish hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1981

Therapy of bladder carcinoma. Long-term results of a retrospective study of 214 cases.

Two hundred and fourteen bladder carcinomas were evaluated retrospectively after reclassification of histological specimens according to UICC. Follow-up time was 7 years or longer. Large size but not multiplicity of the primary tumour indicated a poor prognosis. Local infiltration, even if superficial and restricted to the lamina propria, worsened prognosis as well as high grade of the tumour. Late deaths in the present series were generally explained by a progression in stage in patients with high grade tumours at initial assessment. Therefore a close longterm follow-up should be performed in these patients.

Adult↗
PubMed1983

Bladder carcinoma. Long-term survival and late recurrence.

The records of 115 patients with bladder carcinoma and five years or longer post-diagnosis survival were surveyed after reclassification of the histologic specimens according to UICC. Late recurrence, 5-10 years after the initial diagnosis, was found in 39 patients (34%). Fourteen patients (12%) had died of bladder carcinoma during the observation period, generally as a consequence of transformation to higher tumour stage. Intercurrent disease, i.e. cardiovascular disorders or a second malignancy, led to 21 intercurrent deaths (18%). Large size and high grade of the primary tumour, but not multiplicity, were significantly associated with poorer long-term prognosis. The study underlines the importance of close long-term follow-up of patients with bladder carcinoma in order to permit early detection and treatment or recurrent tumours.

Adult↗
PubMedDate not supplied

Intracytoplasmic immunoglobulins in the differential diagnosis of lymphocytic lymphomas of the B-CLL type and immunocytic lymphomas.

One hundred and thirty-three consecutive cases originally classified either as a lymphocytic lymphoma of the B-CLL type or as an immunocytic (IC) lymphoma could be reclassified morphologically and analyzed for the presence of cytoplasmic immunoglobulins (cIg) with the PAP-technique. The morphologic reclassification confirmed the initial diagnosis in most cases, whereas after staining for cIg, the diagnosis was changed in a large number of cases, i.e. from B-CLL to IC, or the reverse, or from IC of the polymorphic subtype (ICp) to 'high-grade' non-Hodgkin lymphoma (NHL). Cases classified as IC were often localized (stage I+II: 22/43) with a long disease-free survival after local radiation therapy, while B-CLL were usually generalized. For patients in stage IV, the prognosis of B-CLL was significantly superior to that of IC, which in turn was superior to the prognosis of cases referred to as 'high-grade' NHL. The difficulties in the morphologic distinction between B-CLL and IC on one hand and between ICp and some 'high-grade' NHL on the other hand, as well as the clinical significance of these distinctions, are discussed.

Adult↗
PubMed1979

Screening tests for cell-mediated immunodeficiency diseases.

As our knowledge of immunology has become more sophisticated we have had to alter our ideas of the etiology of many immune deficiency diseases. Indeed, current concepts now prevalent have led to reclassification of a number of disease entities. In order to keep our diagnostic efforts abreast of the information being generated by the extensive immunology research programs now in progress, the clinical laboratory has been required to offer a new array of sophisticated tests on a relatively routine basis. This article is intended to serve as a brief review of immunobiology and immunodeficiency diseases with an indepth coverage of specialized tests generally available at the large centers. With an understanding of the principles, procedures, and pitfalls of the tests carried out the laboratory scientist is in a better position to assist the clinician in reaching the correct diagnosis. The detailed review is concerned with methods available to separate, classify, and subclassify lymphocytes and thereby allow a categorization of immune deficiency diseases. Toward that end there is a discussion of surface markers, rosetting, mitogenic and antigenic responsiveness as well as lymphokine production. With a view to present day research tests that might eventually find their way into the armamentarium of the clinical laboratory in the future, there is brief discussion of the methods presently used to classify T-cells as helper, suppressor, or effector cells, assays of some of the lymphokines, and measurement of antibody synthesis in cell culture.

Antigens, Surface↗
PubMed1997

The use of biomarker expression to characterize neoplastic processes.

Biomarkers have been used by pathologists to aid the diagnosis of tumors for almost three decades. Their use has resulted in the re-evaluation and reclassification of several types of tumors. Currently, biomarkers are required to differentiate certain specific tumors with similar histologic patterns. Additional uses of biomarkers in the characterization of neoplastic processes are discussed including their use is prognosis, detecting early neoplastic processes, identifying tumor recurrence, measuring the effectiveness of various therapies (surrogate end point biomarkers), and identifying targets for novel therapies including immunotherapy and gene therapy. We propose that these newer uses of biomarkers will be just as important to pathology in the future as the uses of biomarkers in diagnosis have been over the past two decades.

Biomarkers, Tumor↗