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PubMed2005

Ethics and fraud in science: a review of scientific misconduct and applications to craniofacial research.

The purpose of this article is to review and discuss the occurrence of fraud in biomedical research and analyze the definition, origin, and various forms of scientific misconduct. Fraud in research most often involves reporting data for which no records of experiment or population are present; manipulating research materials, equipment, or procedures to arrive at the desirable result; adding, changing, or omitting results, which positively or negatively relate to the hypothesis that the research intends to test; and incorporating ideas, statements, procedures of others' work without permission and appropriate credit to the source. The etiologic factors contributing to this deviant behavior, and measures taken by relevant bodies to eliminate this phenomenon are discussed. Ethical and integrity aspects of craniofacial research are explored and a set of criteria to facilitate rigorous assessment of the integrity of clinical and basic research protocols is proposed. These include (1) an integrity-focused training of researchers to adhere to specific laboratory procedure and tactics which discourage fraud; (2) appointment of external reviewers to detect unusual and suspicious experimental process or data patterns; and (3) encouragement of multicenter trials. Although it is widely recognized that the sole determinant of scientific misconduct is the individual investigator's integrity, a number of precautions may effectively reduce the prevalence of this event, which may affect the status and trends of biomedical research in general.

Bioethical Issues↗
PubMedDate not supplied

Percutaneous transnasal sphenoidotomy with sphenoid window.

Ten percutaneous transnasal sphenoidotomies were performed in nine children; and in seven, a sphenoid window was also created. All procedures were performed in the special procedures laboratory, with biplane fluoroscopic guidance used in each case. Under general anesthesia, with the child in the supine position, a 14-gauge antral trocar was placed transnasally into the sphenoid sinus. The sinus was aspirated and material was obtained for culture. A Takahashi forceps was placed via the same tract into the sphenoid sinus. The cusps were centered across the anterior cortex, and under fluoroscopic visualization, opened and rotated 360 degrees, creating a sphenoid window. All procedures were completed without complication, and no child required further surgery.

Adolescent↗
PubMedDate not supplied

Laboratory guidelines for blood cultures in Papua New Guinea.

Laboratory procedures for blood culture technology appropriate for Papua New Guinea are described. Included are the selection and use of culture media; the collection, inoculation and incubation of clinical material; the isolation and identification of pathogens; and the referral of isolates for further testing.

Bacteriological Techniques↗
PubMed2002

Application of a 5-bromo-2'-deoxyuridine ELISA for measuring the lymphoproliferative response to human cytomegalovirus in HIV-1-infected patients.

Assessment of the lymphoproliferative response to human cytomegalovirus (HCMV) may help to identify human immunodeficiency virus (HIV)-1-infected patients at high risk of developing HCMV end-organ disease. The tritiated thymidine ([3H]-TdR)-incorporation assay is the gold standard for measuring lymphoproliferative responses, though it is unsuitable as a routine laboratory procedure. An alternative non-radioactive technique, a 5-bromo-2'-deoxyuridine (BrdU) enzyme-linked immunosorbent assay, was applied for measuring T-cell proliferation in response to HCMV. Stimulation of either 1 x 10(5) or 5 x 10(4) peripheral blood mononuclear cells (PBMCs)/well with 10 PFU/well (before inactivation) of inactivated HCMV (AD169 strain) virions during 5 days, followed by an 18 h period of pulsing with BrdU (10 microM) proved to be the optimal laboratory conditions. The assay is simple, economical and feasible for monitoring the lymphoproliferative response to HCMV in HIV-1-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed2006

How much stress do researchers inflict on their study animals? A case study using a scincid lizard, Eulamprus heatwolei.

Research on live vertebrates is regulated by ethics committees, who prohibit ;excessively stressful' procedures. That judgment is based on intuition - a notoriously unreliable criterion when dealing with animals phylogenetically distant from humans. To objectively evaluate the stress imposed by research practices, we measured plasma corticosterone levels in lizards (Eulamprus heatwolei Wells & Wellington, Scincidae). Some procedures (handling and measuring, toe-clipping for identification, exposure to predator scent) did not induce significant increases in corticosterone levels, suggesting that these stimuli generated relatively little stress. However, other stimuli (testing locomotor speed, microchip implantation, blood sampling, an unfamiliar enclosure, tail autotomy, exposure to a heterospecific lizard) were more stressful, with corticosterone levels increasing only transiently in some treatments (<2 h for tail autotomy), but persisting much longer in others (14 days for microchip implantation). Overall, our data suggest that the levels of stress induced by routine laboratory procedures are no greater than those often experienced by lizards in nature; but that intuition provides a poor basis for evaluating the levels of stress induced by research. For example, toe-clipping is often criticized and sometimes banned; but our data suggest that this method is actually less stressful than the technique frequently recommended to replace it on ethical grounds (microchip implantation). Toe-clipping also was less stressful than superficially trivial manipulations such as housing the animal in an unfamiliar enclosure. More generally, we urge researchers to seek objective information on the effects of their activities on research subjects, rather than relying upon subjectivity and anthropomorphism in making these evaluations.

Acclimatization↗
PubMed1988

Cerebrospinal fluid.

It is hoped that we have demonstrated that collection, handling, and limited analysis of CSF samples from the dog and cat are relatively simple. No special equipment or handling is required, and the procedures are within the capabilities of any veterinarian interested in performing them. In addition, although this article was not intended to present a detailed discussion on the interpretation of the analysis of CSF, we have demonstrated some very practical interpretations to the various aspects of a routine CSF analysis. When combined with a signalment, complete history, and thorough general physical and neurologic examination, CSF analysis can prove invaluable in the workup of an animal with a neurologic disorder. Relatively simple laboratory procedures can be helpful in differentiating peripheral blood contamination from true intrathecal hemorrhage, in identifying an active inflammatory process, in potentially characterizing an etiologic agent, and, on rare occasions, in identifying primary or metastatic neoplastic disease involving the CNS. In many cases, the above is not directly possible, because the changes observed in our routine analysis are nonspecific. Yet, documenting and following these "nonspecific" alterations are helpful in determining if there is progression or regression of the disease process. In turn, these changes or lack of changes are helpful in identifying if the proper therapy has been instituted and if additional or different therapy is required.

Animals↗
PubMed1983

Impact of a cost-containment educational program on housestaff ambulatory clinic charges.

A cost-containment project was established to determine if a broad educational program that coupled clinical logic with feedback of charges to internal medicine residents in an ambulatory clinic setting could alter behavior. The project was evaluated by comparing charge data from a preintervention comparison year with charge data from the intervention year. Decreases in charges for laboratory procedures occurred in six of the seven diagnostic categories during intervention and were significant (t-test) for four categories. Regression analysis evaluated the influence of the intervention and 12 other variables on charges and demonstrated that the intervention was associated with a mean reduction of lab charges of $ 6.30 (p less than 0.0001) and a mean reduction of total encounter charges of $ 10.36 (p less than 0.01). We conclude that our educational program resulted in a decrease in mean laboratory changes and total charges for ambulatory encounters.

Awareness↗
PubMedDate not supplied

Fundamentals of computerised data acquisition in the human performance laboratory.

Researchers of the future will depend upon computer technology to address questions that previously could not be answered using traditional methods of data acquisition. Recent advances in computer design and software availability have eliminated many of the limitations previously associated with computer use in the laboratory setting. Although computerisation facilitates the acquisition of laboratory data, identification of errors introduced into the measurement is often more difficult. The laboratory computer is only one component of an automated data acquisition system. A system designed to collect physiological data comprises several primary components, including: (a) sensing element; (b) signal amplification/conditioning circuits; (c) analogue display; (d) computer interface; (e) laboratory computer; and (f) acquisition software. The acquisition and conditioning of analogue signals is accomplished using traditional laboratory procedures familiar to the researcher. Converting this analogue signal into a digital format used by the computer, however, represents new techniques. Fundamentals of computerised data acquisition are discussed. An understanding of how an automated data acquisition system is configured and the techniques used to transform the values will assist the user in identifying sources of error introduced into the measurement. Additionally, familiarization with the methods of computerisation will provide insight into future applications of computer technology in the human performance laboratory.

Analog-Digital Conversion↗
PubMed1991

Representation of clinical laboratory terminology in the Unified Medical Language System.

The Unified Medical Language System (UMLS) was examined to determine its coverage of clinical laboratory terminology in use at the Columbia-Presbyterian Medical Center (CPMC). The Metathesaurus (Meta-1) contains exact matches for 30% of 1460 CPMC laboratory terms and near matches for an additional 42%, with better coverage of atomic-level concepts ("substance" terms) than complex ones (tests and panels). The Semantic Network includes types for representing laboratory procedures (2), measured substances (at least 56) and sampled substances (at least 14), but no type to represent specimens. Few of the UMLS semantic relationships are applicable to the CPMC vocabulary. These results have implications for the utility of the UMLS for linking clinical databases to electronic medical information sources.

Clinical Laboratory Techniques↗
PubMed1989

Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus.

The protein (Western) immunoblot assay (IB) for antibodies to human immunodeficiency virus, like other laboratory procedures, sometimes gives variable results. In the Transfusion Safety Study, indistinguishable aliquots of four quality control (QC) samples have been routinely submitted for IB with each group of patient specimens. A false negative IB result was obtained for 1.7% of 179 assays of two known positive (QC) standards and a false positive result for 2.0% of 101 assays of two known negative (QC) standards. In addition, a test panel of 24 samples was sent on a single occasion to three widely used laboratories. A false positive result was reported by one laboratory and a false negative by a second. Although generally reliable, IB results may occasionally be in error. There is much more technical variability in the relative frequencies of antigen-antibody bands than has been recognized. These interlaboratory and intralaboratory comparisons show quality control checks are essential for all laboratories, and more than one specimen should be tested if its applicability to a specific patient is questionable. Specific bands are sufficiently inconstant for the same specimen to make appearance or disappearance on successive specimens prognostically unreliable.

Blotting, Western↗
PubMed2004

Socio-economic differences and health seeking behaviour for the diagnosis and treatment of malaria: a case study of four local government areas operating the Bamako initiative programme in south-east Nigeria.

BACKGROUND: Malaria is one of the leading causes of mortality and morbidity in Nigeria. It is not known how user fees introduced under the Bamako Initiative (BI) system affect healthcare seeking among different socio-economic groups in Nigeria for diagnosis and treatment of malaria. Reliable information is needed to initiate new policy thrusts to protect the poor from the adverse effect of user fees. METHODS: Structured questionnaires were used to collect information from 1594 female household primary care givers or household head on their socio-economic and demographic status and use of malaria diagnosis and treatment services. Principal components analysis was used to create a socio-economic status index which was decomposed into quartiles and chi-square for trends was used to calculate for any statistical difference. RESULTS: The study showed that self diagnosis was the commonest form of diagnosis by the respondents. This was followed by diagnosis through laboratory tests, community health workers, family members and traditional healers. The initial choice of care for malaria was a visit to the patent medicine dealers for most respondents. This was followed by visit to the government hospitals, the BI health centres, traditional medicine healers, private clinics, community health workers and does nothing at home. Furthermore, the private health facilities were the initial choice of treatment for the majority with a decline among those choosing them as a second source of care and an increase in the utilization of public health facilities as a second choice of care. Self diagnosis was practiced more by the poorer households while the least poor used the patent medicine dealers and community health workers less often for diagnosis of malaria. The least poor groups had a higher probability of seeking treatment at the BI health centres (creating equity problem in BI), hospitals, and private clinics and in using laboratory procedures. The least poor also used the patent medicine dealers and community health workers less often for the treatment of malaria. The richer households complained more about poor staff attitude and lack of drugs as their reasons for not attending the BI health centres. The factors that encourage people to use services in BI health centres were availability of good services, proximity of the centres to the homes and polite health workers. CONCLUSIONS: Factors deterring people from using BI centres should be eliminated. The use of laboratory services for the diagnosis of malaria by the poor should be encouraged through appropriate information, education and communication which at the long run will be more cost effective and cost saving for them while devising means of reducing the equity gap created. This could be done by granting a properly worked out and implemented fee exemptions to the poor or completely abolishing user fees for the diagnosis and treatment of malaria in BI health centres.

Journal Article↗
PubMed2005

A case refort of Sandhoff disease.

Sandhoff disease is a rare autosomal recessive metabolic disease presenting bilateral optic atrophy and a cherry red spot in the macula. This case report presents the characteristics of a patient with Sandhoff disease as assessed by ophthalmic, neuroimaging, and laboratory procedures. Ophthalmologic examination revealed that the patient could not fixate her eyes on objects nor follow moving targets. A pale optic disc and a cherry red spot in the macula were seen in both eyes. Low signal intensity at the thalamus and high signal intensity at the cerebral white matter were noted in a T2-weighted brain MR image. A lysosomal enzyme assay using fibroblasts showed the marked reduction of both total beta-hexosaminidases, A and B. Based on the above clinical manifestations and laboratory findings, we diagnosed the patient as having Sandhoff disease.

Atrophy↗
PubMed1987

Laboratory evaluation for Cushing's syndrome in psychiatric patients with cortisol nonsuppression following the overnight dexamethasone suppression test.

Laboratory tests used for the differential diagnosis of Cushing's syndrome have infrequently been employed in investigations of psychiatric patients who demonstrate hypothalamic-pituitary-adrenal (HPA) overactivity, and these laboratory procedures have not previously been applied for the specific purpose of further evaluating the endocrine function of psychiatric patients with serum cortisol nonsuppression following the standard 1-mg overnight Dexamethasone Suppression Test (DST). Low-dose (4 mg/48 hr) and high-dose (16 mg/48 hr) DSTs were administered to 10 psychiatric patients who exhibited cortisol nonsuppression after the overnight DST. Patients all had normal suppression to both the low-dose and high-dose tests. HPA overactivity in these patients was thus not sufficient to meet laboratory criteria for the diagnosis of Cushing's syndrome. Study results suggest that psychiatric patients with abnormal cortisol suppression following the 1-mg overnight DST are likely to have normal responses when assessed by standard laboratory protocols used for the diagnosis of Cushing's syndrome.

Adrenocortical Hyperfunction↗
PubMed1993

Evaluation of an outbreak of foodborne illness initiated in the emergency department.

STUDY OBJECTIVES: For many foodborne outbreaks, the pathogen and food vehicle never are identified. Delayed collection of epidemiologic and microbiologic information may contribute to this. We postulated that collection of this information from ill persons as they presented to the emergency department during a recent outbreak might contribute to earlier identification of the pathogen and vehicle. DESIGN: At least 690 of 1,900 conventioneers developed gastrointestinal symptoms after attending a banquet. A questionnaire was developed to collect information on specific food histories, incubation periods, symptoms, physical findings, and demographics. These results were compared with results of investigations by the city and state departments of public health. SETTING: The ED of Rush-Presbyterian-St Luke's Medical Center, a tertiary care university hospital in Chicago, Illinois. TYPE OF PARTICIPANTS: Adults (24 men and nine women) presenting to the ED with gastrointestinal symptoms after eating a common meal. MEASUREMENTS AND MAIN RESULTS: The clinical syndrome suggested an invasive pathogen. Based on this, clinical microbiology laboratory procedures were modified (isolation plates were reviewed during the evening shift). This led to early identification of the first isolates (Salmonella enteritidis) from the outbreak. The questionnaire also narrowed the vehicle to one of two foods served. Investigations by the departments of public health subsequently identified one of these, bread pudding with a raw egg based-sauce, as the vehicle. CONCLUSION: Outbreak evaluations can begin in the ED or any other patient care facility. This evaluation need not always add significantly to the expenditure of time, manpower, or laboratory studies. The evaluation of even a small percentage of ill persons from a large outbreak may provide useful epidemiologic information and be particularly important in settings with limited public health resources.

Adult↗
PubMed2004

Clinical outcome of the altered cast impression procedure compared with use of a one-piece cast.

STATEMENT OF THE PROBLEM: An altered cast impression procedure to improve the support of distal extension removable partial dentures is widely taught, but not often used in dental practice. PURPOSE: The purpose of this study was to determine the efficacy of an altered cast compared to a one-piece cast with regard to base support, abutment health, and patient comfort over time. MATERIAL AND METHODS: Seventy-two patients receiving a mandibular bilateral distal extension removable partial denture were assigned randomly for treatment using either a one-piece or an altered cast. All impressions and associated laboratory procedures were made by one investigator. A second investigator evaluated extension, support, and adaptation of the denture bases by observation of border length and lifting of the indirect retainer from its seat. The space between the soft tissues and the base when the framework was related to the teeth was measured cross-sectionally at half the length of the denture base. Mobility, gingival index, and sulcus depths at 6 locations around each abutment tooth were recorded at insertion and again 1 year later. Chi-square tests were used to evaluate differences between the treatment groups (alpha=.05). RESULTS: There was 0.15 mm less space between the ridge crest and base in the altered cast group (P<.01), and underextension of the base occurred only in the one-piece cast group (P=.01). At insertion, no tissue-ward movement was observed in 85% of the prostheses when anterior-posterior rotation was attempted. Fifteen subjects (21%) were lost to recall at 1 year, but they were distributed equally between the 2 groups. Of the remaining 57 prostheses, 42% exhibited decreased base support and 33% had increased gingival inflammation; the deepest probing depth decreased in 61%, mobility decreased or remained the same in 80% of the direct abutments, and 88% of the subjects were satisfied. None of these findings were related to the impression procedure. CONCLUSION: The altered cast impression procedure does not offer significant advantages over the one-piece cast, provided the standards used in this study are met. These include a completely extended impression, use of magnification to adjust and ensure complete seating of the framework, and coverage of the retromolar pad and buccal shelf by the base.

Adult↗
PubMed2006

Radiogenic argon distribution within a mineral grain: implications for dating of hydrothermal mineral-forming event in Sludyanka complex, Siberia, Russia.

Usually, in age-determination procedures, the experimenter is interested in the mean concentrations of parent and daughter substances. However, the structure of a solution of the Fick's diffusion equation enables one to specify a procedure, allowing, through macroscopic experiments, one to determine the distribution of radiogenic argon (as well as any of other isotopes) within a mineral grain. Argon, influenced in the geological past by a metamorphic event, has a half-sinusoidal distribution, whereas argon preserved in geological time has a rectangular distribution. The ratio of the quantity of argon of the first type to the total argon is called an alpha-factor. It is believed that this coefficient can be of great interest for geochronological studies, being a symptom of virtual Ar losses and the time instant, at which they happened. A laboratory procedure and a mathematical algorithm to determine the alpha-factor are developed. As an example, a determination of the alpha-factor on a vein-phlogopite from the well-studied Sludyanka deposit, Southern Baikal, Siberia, Russia, is described. Rb-Sr isochron age on phlogopite-calcite-apatite paragenetic assemblage yielded 460+/-7 Ma and is constrained by U-Pb zircon ages of 471+/-1 and 447+/-2 Ma, respectively, on an emplacement of early syenites and monzonites and later 'post-phlogopitic' pegmatites [E.B. Salnikova, S.A. Sergeev, A.B. Kotov, S.Z. Yakovleva, R.H. Steiger, L.Z. Reznitskiy, E.P. Vasil'ev. U-Pb zircon dating of granulite metamorphism in the Sludyanskiy complex, Eastern Siberia. Gondwana Res., 1, 195-205 (1998). L.Z. Reznitskii, G.P. Sandimirova, Y.A. Pakhol'chenko, S.V. Kuznetsova. The Rb-Sr age of phlogopite deposits in Sludyanka, southern Baikal region. Dokl. Earth Sci., 367, 711-713 (1999). L.Z. Reznitskii, A.B. Kotov, E.B. Salnikova, E.P. Vasil'ev, S.Z. Yakovleva, V.P. Kovach, A.M. Fedoseenko. The age and time span of the origin of phlogopite and lazurite deposits in the Southwestern Baikal area: U-Pb geochronology. Petrology, 8, 66-76 (2000).]. In this study, the phlogopite gave an apparent K-Ar age of 365.6+/-10.4 Ma which has no geological meaning. The alpha-factor of 0.27 was derived from a laboratory kinetic experiment. The age determined by the rectangularly distributed argon corresponded to alphax0.129 nmm3/g (total radiogenic argon in the sample)=94.17 nmm3/g, and an age of approximately 274 Ma (e.g. a period without any argon losses). Here, at the first sight, we deal with common argon losses not conjugated with any geological event, because after 447 Ma only lower temperature (in a range of 50-300 degrees C) hydrothermal processes were recorded. A paragenetic phlogopite-bearing vein mineral, hyalophane, having a disturbed Rb-Sr isotopic system, however, yielded 40Ar/39Ar subplateau age of 271+/-2 Ma [V.V. Ivanenko, M.I. Karpenko, M.A. Litsarev. Age of the Sludyanka phlogopite deposits (in Russian; data of the 39Ar-40Ar method). In Geological Series 5, pp. 92-98, Izvestiya Akademii Nauk SSSR, Moskva (1990).], marking similar timing of the K-Ar isotopic system closure. This indicates that K-Ar isotopic system in the phlogopite was not closed (or was partially reset) long after its crystallisation and closing of the Rb-Sr system, in spite of the fact that the crystal was not affected by processes having temperatures above the accepted closure temperatures for micas. There seems to have acted an exchange mechanism of OH-groups between surrounding fluid and hydrocrystal structure. Thus the argon loss did not occur, spontaneously, but argon particles seem to have been captured and carried to the mineral surface by vacancies formed during displacements of OH-groups.

Argon↗
PubMed1999

Extensive cross-contamination of specimens with Mycobacterium tuberculosis in a reference laboratory.

A striking increase in the numbers of cultures positive for Mycobacterium tuberculosis was noticed in a mycobacterial reference laboratory in Campinas, Sao Paulo State, Brazil, in May 1995. A contaminated bronchoscope was the suspected cause of the increase. All 91 M. tuberculosis isolates grown from samples from patients between 8 May and 18 July 1995 were characterized by spoligotyping and IS6110 fingerprinting. Sixty-one of the 91 isolates had identical spoligotype patterns, and the pattern was arbitrarily designated S36. The 61 specimens containing these isolates had been processed and cultured in a 21-day period ending on 1 June 1995, but only 1 sample was smear positive for acid-fast bacilli. The patient from whom this sample was obtained was considered to be the index case patient and had a 4+ smear-positive lymph node aspirate that had been sent to the laboratory on 10 May. Virtually all organisms with spoligotype S36 had the same IS6110 fingerprint pattern. Extensive review of the patients' charts and investigation of laboratory procedures revealed that cross-contamination of specimens had occurred. Because the same strain was grown from all types of specimens, the bronchoscope was ruled out as the outbreak source. The most likely source of contamination was a multiple-use reagent used for specimen processing. The organism was cultured from two of the solutions 3 weeks after mock contamination. This investigation strongly supports the idea that M. tuberculosis grown from smear-negative specimens should be analyzed by rapid and reliable strain differentiation techniques, such as spoligotyping, to help rule out laboratory contamination.

Bacteriological Techniques↗
PubMed1951

Diagnosis of pulmonary coccidioidal infections.

A wide variety of pulmonary lesions may be caused by coccidioidomycosis. Suspicion of coccidioidomycosis may be substantiated by careful clinical-epidemiological histories. The first laboratory procedure should be a coccidioidin skin test. If the reaction to the test is positive, serological tests are next. Also, if there is no reaction to coccidioidin, serological tests are still indicated if dissemination is suspected. The more severe the infection, the greater the probability of establishing a diagnosis serologically. In only three-fifths of patients with coccidioidal cavities can the diagnosis be fixed serologically. In such patients if differential skin tests are not conclusive, attempt should be made to recover the fungus. However, this is accompanied by great risk of laboratory infection. Eosinophilia and accelerated erythrocyte sedimentation are only circumstantial items of evidence, as is the appearance of the pulmonary roentgenogram.

Blood Sedimentation↗