RESUMEN
OBJECTIVE: To determine the impact of a health system-wide fetal fibronectin (fFN) testing programme on the rates of hospital admission for preterm labour (PTL). DESIGN: Multiple baseline time-series design. SETTING: Canadian province of Ontario. POPULATION: A retrospective population-based cohort of antepartum and delivered obstetrical admissions in all Ontario hospitals between 1 April 2002 and 31 March 2010. METHODS: International Classification of Diseases codes in a health system-wide hospital administrative database were used to identify the study population and define the outcome measure. An aggregate time series of monthly rates of hospital admissions for PTL was analysed using segmented regression models after aligning the fFN test implementation date for each institution. MAIN OUTCOME MEASURE: Rate of obstetrical hospital admission for PTL. RESULTS: Estimated rates of hospital admission for PTL following fFN implementation were lower than predicted had pre-implementation trends prevailed. The reduction in the rate was modest, but statistically significant, when estimated at 12 months following fFN implementation (-0.96 hospital admissions for PTL per 100 preterm births; 95% confidence interval [CI], -1.02 to -0.90, P = 0.04). The statistically significant reduction was sustained at 24 and 36 months following implementation. CONCLUSIONS: Using a robust quasi-experimental study design to overcome confounding as a result of underlying secular trends or concurrent interventions, we found evidence of a small but statistically significant reduction in the health system-level rate of hospital admissions for PTL following implementation of fFN testing in a large Canadian province.
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Fibronectinas/metabolismo , Trabajo de Parto Prematuro/diagnóstico , Admisión del Paciente/tendencias , Atención Prenatal/métodos , Biomarcadores/metabolismo , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Trabajo de Parto Prematuro/metabolismo , Ontario , Evaluación de Procesos y Resultados en Atención de Salud , Admisión del Paciente/estadística & datos numéricos , Embarazo , Atención Prenatal/normas , Análisis de Regresión , Estudios RetrospectivosRESUMEN
AIMS: To evaluate if clinical practice guideline recommendations regarding self-monitoring of blood glucose in patients with diabetes not using insulin follow the principles of evidence-based medicine. METHODS: After a search from 1999 to 2011, 18 clinical practice guidelines were included. Recommendations regarding self-monitoring of blood glucose were graded on a scale from one (strongly against self-monitoring) to four (strongly in favour of self-monitoring) and compared with the similarly graded conclusions of systematic reviews that were cited by the clinical practice guidelines. We also investigated how clinical practice guideline characteristics, for example funding sources, and quality of references cited could be related to the guideline recommendations. RESULTS: The clinical practice guidelines cited in total 15 systematic reviews, 14 randomized controlled trials, 33 non-randomized controlled trials papers and 18 clinical practice guidelines or position statements. The clinical practice guideline recommendations had an average grade of 3.4 (range 2.0-4.0). Higher grades were seen for clinical practice guidelines that acknowledged industry funding (mean value 4.0) or were issued by organizations depending on private funding (mean value 3.6 vs. 3.0 for governmental funding). The conclusions of the 15 systematic reviews had a mean grade of 2.2 (range 1.0-3.8). Systematic reviews with low grades were less cited. In total, 21 randomized controlled trials were included in the systematic reviews. Approximately half of these evaluated an educational intervention where the effect of self-monitoring of blood glucose could not be clearly isolated. CONCLUSIONS: Clinical practice guidelines were more in favour of self-monitoring use than the systematic reviews that were cited. The citation practice was non-systematic and industry funding seemingly led to a more positive attitude towards use of self-monitoring of blood glucose.
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Automonitorización de la Glucosa Sanguínea , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicina Basada en la Evidencia , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Masculino , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The use of the prostate-specific antigen (PSA) test has been increasing rapidly in Canada since its introduction in 1988. The reasons for using the PSA test in patients without known prostate cancer are unclear. This paper reports on the first study in Canada to use physician records to assess the use of PSA testing. METHODS: A questionnaire was mailed to physicians attending 475 patients without diagnosed prostate cancer. The patients were randomly selected from 2 laboratory databases of PSA test records in the greater Toronto area during 1995. The physicians were asked to consult their patient records to avoid recall bias. Information obtained included physician's specialty, patient's age at time of PSA test and reason(s) for the test. RESULTS: There were 264 responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95% confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical procedure or drug therapy. More than one reason was permitted. Of 151 responses indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part of a routine examination. For 19%, both investigation of symptoms and screening asymptomatic patients were given as reasons for testing, and for another 19% both follow-up of a medical procedure and screening were given as reasons. Screening was recorded as a reason for testing far more commonly for patients seen by family physicians and general practitioners than for patients seen by urologists (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary symptoms was more common for patients seen by urologists than for those seen by family physicians and general practitioners (52% v. 37%, p = 0.044). No significant difference was found between physician groups in the use of PSA testing as a follow-up of a medical procedure (42% for urologists and 31% for family physicians and general practitioners). About 24% of the PSA test records were for patients younger than 50 and older than 70 years. PSA testing initiated by patients was more common in the practices of family physicians and general practitioners than in the practices of urologists (44% v. 13%, p < 0.001). INTERPRETATION: Screening for prostate cancer was the most common reason for PSA testing in our study group; it occurred most commonly in the family and general practice setting and was usually initiated by the patient. Differences in reasons for testing were identified by practice specialty. Although PSA screening for prostate cancer is sometimes recommended for men between 50 and 70 years of age, it is being conducted in men outside this age group.
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Biomarcadores de Tumor/sangre , Tamizaje Masivo , Pautas de la Práctica en Medicina/estadística & datos numéricos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Medicina Familiar y Comunitaria , Encuestas de Atención de la Salud , Humanos , Masculino , Medicina , Persona de Mediana Edad , Ontario , EspecializaciónAsunto(s)
Fosfatasa Ácida/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Próstata/diagnóstico , Humanos , Masculino , Estadificación de Neoplasias , Próstata/enzimología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Curva ROC , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: To ascertain the extent of prostate-specific antigen (PSA) testing in patients with prostate cancer (PC), with other cancers (OC), and with no cancer (NC) in two clinical laboratory databases. DESIGN AND METHODS: PSA test records were obtained from a tertiary care hospital, Sunnybrook Health Science Centre (SHSC) and from a private laboratory, Gamma-Dynacare Medical Laboratories (GDL), during the period 1988 to 1995. These records were linked with the Ontario Cancer Registry (OCR) to establish a diagnosis of PC, OC, or NC. Trends in PSA testing according to diagnostic category, testing laboratory, patient age (by decade), and PSA value (in microgram/L) were determined. RESULTS: Major cancer sites identified in the patients tested for PSA were prostate (60%), bladder and colon (7% each), lung (5%), kidney (3%), and rectum (3%). There were 11,867 patients (8.5%) with PC, 8,002 (5.9%) with OC, and 118,954 (86%) with NC. The total number of PSA tests performed on these patients was 230,756, of which 21% were on PC, 5% on OC, and 74% on NC; of these tests, 64% were performed through GDL and 36% through SHSC. The mean (median) number of tests per patient was: PC, 4.0 (2); OC, 1.4 (1); and NC, 1.5 (1). For PC 89% and for OC 72% of all tests occurred after diagnosis. Between 1990 and 1995 the number of PSA tests increased two-fold in PC and OC, and 20-fold in NC. We estimate that about one-half of the PSA tests in the NC group were for screening purposes. The proportion of PSA tests occurring in PC, OC, and NC for patients 50 to 70 years of age was 41%, 50%, and 63%, respectively; for patients over 70 years of age, this proportion was 58%, 46%, and 22% respectively; and for patients under 50 it was 1%, 4%, and 15%, respectively. Between 1990 and 1995, the largest increase in testing frequency was in the NC group, particularly in patients 50 to 70 years of age, which was accompanied by a decrease in patients over 70. Less than 10% of testing occurred in patients under 50 in all diagnostic groups. We estimate that about 26% of PSA screening tests in NC occurred outside the guidelines for patient age. Between 1988 and 1995, the proportion of PSA results below our detection limit (< 0.2 micrograms/L) showed a steady rise in the PC group, as did the proportion between 0.2 and 3.9 micrograms/L; these were accompanied by a fall in the proportion > 20.0 micrograms/L. However, the proportion of PSA results within these ranges did not change much during the same time period for the OC and NC groups. At cutoffs of PSA = 4.0 micrograms/L (or PSA = 10.0 micrograms/L), estimates of clinical specificity were 84.0% (or 96.3%), and of clinical sensitivity were 83.4% (or 47.1%). CONCLUSIONS: Most (86%) PSA testing occurred in men with NC, consistent with diagnosis or screening. There were more PSA tests per patient in PC than in OC, and most testing occurred after diagnosis. PSA testing in the NC group continues to increase rapidly. The proportion of PSA tests in patients over age 70 decreased in the order of PC > NC > OC. Between 1990 and 1995, there was an increase in the proportion of patients tested who were between 50 and 70 in the NC group, which may suggest more screening in this group. Over this same time period, there was an increase in the proportion of undetectable PSA values, possibly suggesting increased use of radical therapy; there was also a decrease in the proportion of PSA > 20 micrograms/L, possibly suggesting a decrease in the prevalence of advanced stage PC.
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Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Factores de Edad , Anciano , Bases de Datos Factuales , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Ontario , Neoplasias de la Próstata/química , Distribución TisularRESUMEN
OBJECTIVES: The range of "normal" prostate-specific antigen (PSA) values compatible with cure following radiotherapy (RT) for prostate cancer (PCa) has yet to be established. Various thresholds, ranging from 0.5 to 4.0 ng/mL are used to define biochemical disease-free status. Because the proportion of free PSA is lower in men with PCa, the ratio of free PSA to total PSA could theoretically be useful in determining cancer-free status after RT. METHODS: One hundred two men treated with standard external beam RT from October 1988 to October 1994 (median dose, 66 Gy) were chosen for measurement of percent free PSA because they had a routine follow-up visit in November or December of 1996. All patients had undergone systematic transrectal ultrasound-guided biopsies after RT. Biopsies were negative in 66 patients, positive in 21, and indeterminate in 15 (rare, degenerated cancer cells with no evidence of proliferation by immunohistochemical stains). Stage distribution was T1b, 8; T1c, 9; T2a, 25; T2b/c, 40; and T3, 20. Median follow-up is 40 months. RESULTS: Total serum PSA ranged from 0. 1 to 10.0 ng/mL. Because the mean (+/-SD) percent free PSA for patients with negative (n = 66) and indeterminate (n = 15) biopsies were 29% +/- 18% and 25% +/- 7%, respectively (P = 0.13), these were combined. The mean (+/-SD) percent free PSA for those with positive biopsies (n = 21) was 15% +/- 8% and was significantly different from those with negative or indeterminate biopsies (P < 0.001). Patients with negative or indeterminate biopsies were grouped according to their total PSA as 0.1 to 0.5 ng/mL (n = 33), 0.6 to 1.0 ng/mL (n = 23), 1.1 to 2.0 ng/mL (n = 17), and greater than 2.0 ng/mL (n = 7). The mean percent free PSAs were 34%, 28%, 21%, and 12%, respectively. CONCLUSIONS: Percent free PSA may be a useful adjunct in diagnosing recurrent PCa after RT. The ratio is significantly different in patients of known biopsy status, distinguishing a group with positive biopsies from those with negative. However, there is overlap in individual values, and because patients with negative biopsies after RT may have subclinical distant disease, more follow-up is necessary before percent free PSA can be incorporated into a definition of biochemical disease-free status. Percent free PSA may be most useful for PSA from 0.6 to 2.0 ng/mL, where failure is common, but not universal.
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Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Estudios de Seguimiento , Humanos , Masculino , Estudios ProspectivosAsunto(s)
Laboratorios , Antígeno Prostático Específico/sangre , Estudios de Seguimiento , Humanos , Laboratorios/estadística & datos numéricos , Laboratorios/tendencias , Laboratorios de Hospital/estadística & datos numéricos , Laboratorios de Hospital/tendencias , Estudios Longitudinales , Masculino , Ontario/epidemiología , Neoplasias de la Próstata/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To provide a general outline for a 2-year postdoctoral training program in clinical chemistry, and a detailed outline of the first year laboratory training program. METHODS & RESULTS: Essential elements of the 2-year Postdoctoral Training Program in Clinical Chemistry at the University of Toronto are its didactic courses and a comprehensive, structured laboratory rotation in the first year. Residents rotate in hospital laboratories in both years of the Program. The hospital laboratory rotation in first year includes a 36-week laboratory rotation based on the Laboratory Training Program Manual. In the second year, they consolidate the basic knowledge acquired in first year and gain experience in pediatric testing and other specialty areas. In both years, residents attend teaching and ward rounds on a regular basis, investigate unusual test requests and patient results, and make regular presentations at case presentation and journal club sessions. They undertake research and development projects which lead to presentations at scientific meetings and to publication. Residents attend departmental management meetings, arrange discussions on management topics, and attend a short course on key management topics. Approaches for strengthening the knowledge and skills of residents in the areas of hematology, microbiology and pathology are being developed. CONCLUSION: The program outline described should provide a useful framework for other such programs both nationally and internationally.
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Centros Médicos Académicos , Química Clínica/educación , Educación de Postgrado , Canadá , Certificación , CurriculumRESUMEN
OBJECTIVE: To review the factors that affect the concentration of prostate specific antigen (PSA) in the serum. RESULTS: The discussion includes the structure of PSA; its distribution and metabolism; various analytical aspects of PSA measurements; the effects of clinical manipulations on PSA, including digital rectal examination, transrectal ultrasound, cystoscopy, biopsy and transurethral resection of the prostate; factors affecting PSA levels in health, in benign disease, and in prostate cancer; the effect of various treatments on PSA; and the issue of reference ranges. CONCLUSION: Laboratory staff and physicians must take many factors into consideration when interpreting PSA results.
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Antígeno Prostático Específico/sangre , Enfermedades de la Próstata/metabolismo , Humanos , Masculino , Antígeno Prostático Específico/química , Antígeno Prostático Específico/fisiología , Enfermedades de la Próstata/terapiaRESUMEN
OBJECTIVE: To investigate the effects of chronic calcium pyrophosphate dihydrate (CPPD) synovitis on the development of osteoarthritic (OA) lesions in an animal model. METHODS: OA was induced in the right knees of 30 male New Zealand white rabbits by partial lateral meniscectomy and section of the fibular collateral and sesamoid ligaments (PLM/LS), followed by 8 weekly intraarticular (IA) injections of 1 mg (low-dose) or 10 mg (high-dose) of CPPD crystals in 3 sets of experiments (10 rabbits each). The contralateral left knees served as controls: experiment 1 PLM/LS alone, experiment 2 8 weekly IA injections of CPPD crystals alone, and experiment 3 sham surgery plus 8 weekly IA injections of CPPD crystals. RESULTS: At 8 weeks, repeated IA injections of low-dose and high-dose CPPD crystals into meniscectomized right knees resulted in more severe OA than in meniscectomized but noninjected left knees (experiment 1) (P = 0.003 and P = 0.001, respectively). One-fourth of the meniscectomized knees (11 of 40), both CPPD-injected and noninjected, showed embedded synovial cartilage shards. CONCLUSION: The data demonstrate a worsening effect of chronic CPPD crystal-induced synovitis on experimental OA produced in the rabbit knees by PLM/LS, and support a possible role for CPPD microcrystalline inflammation in the progression of OA lesions in clinical CPPD crystal deposition disease.
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Condrocalcinosis/complicaciones , Sinovitis/complicaciones , Animales , Cartílago Articular/patología , Condrocalcinosis/fisiopatología , Modelos Animales de Enfermedad , Articulación de la Rodilla/patología , Masculino , Meniscos Tibiales/cirugía , Osteoartritis/etiología , Conejos , Sinovitis/fisiopatologíaRESUMEN
The Canadian Health Care System is operated governmentally at the provincial level although the costs and benefits are similar in every province. Most physicians are remunerated on the 'charge per service' basis, but laboratory physicians (including medical biochemists) are among the few who are remunerated by salary. The training of medical biochemists is regulated by the Royal College of Physicians and Surgeons of Canada by means of a residency program of 4 years duration, following graduation from medical school and completion of the required internship. The training of clinical biochemists, whose functions overlap many of those attributable to medical biochemists, is regulated by the recently created Canadian Academy of Clinical Biochemistry through a certification process incorporating written and oral examinations approximately 1 year apart. Recognized and accredited training programs for clinical biochemists exist in several medical schools: these courses are of 2 (occasionally 3) years duration and entry to these programs requires a Ph.D. and, preferably, some post-graduate research experience. Details of both medical and clinical biochemistry training programs reveal a difference in emphasis and duration rather than in course content, with medical trainees required to spend at least 1 of their 4 training years in clinical disciplines relevant to the practise of biochemistry.
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Química Clínica/educación , Bioquímica/educación , Canadá , Curriculum , Educación de Postgrado en Medicina , Laboratorios/organización & administración , Laboratorios/normasRESUMEN
We have developed 2 new quantitative methods for measuring anti-p53 antibodies in human serum. Using these methods we analyzed 1,392 sera from patients with various malignancies and 230 sera from individuals without malignancy. Highest prevalence of anti-p53 antibodies was associated with ovarian and colon cancers (15%), followed by lung (8%) and breast (5%) cancers. Prevalence in other malignancies was lower (< 4%). In hospitalized patients and apparently healthy individuals, prevalence was very low (< 2 and 1% respectively). Extremely high antibody concentrations (> 10(5) U/L) were found in 5 ovarian, 2 breast, 1 lung and 1 colon cancers. Sequential analysis of 6 positive samples has shown that the p53 antibody test may have potential for patient monitoring. The p53 antibody-positive sera from breast cancer patients were associated with tumors that were steroid hormone receptor-negative (p < 0.002). We propose that the measurement of p53 antibodies is a relatively specific serological test for cancer, which can be performed with easily automatable and quantitative methodologies and may be further exploited for patient monitoring, prognosis, diagnosis and probably screening for selected cancers.
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Anticuerpos Antineoplásicos/sangre , Neoplasias/inmunología , Proteína p53 Supresora de Tumor/inmunología , Anciano , Western Blotting , Neoplasias Encefálicas/inmunología , Antígeno Carcinoembrionario/análisis , Neoplasias del Colon/inmunología , Femenino , Humanos , Métodos , Persona de Mediana Edad , Neoplasias Ováricas/inmunología , PronósticoRESUMEN
A total of 23 women with stage II breast cancer receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil had detailed pharmacokinetic monitoring performed on the first and third courses of therapy. The area under the concentration time curve (AUC) of each of these three drugs varied by a factor of 3-4 among patients. No systematic change in pharmacokinetics between the first and third courses was seen for cyclophosphamide, methotrexate or 5-fluorouracil, and the mean AUC for each of the three drugs did not change. However, significant intrapatient variability in drug pharmacokinetics was observed for all three drugs such that the AUC, clearance and half-life in an individual on the third course could not be reliably predicted from data generated on the first course. On the basis of these results, cyclophosphamide, methotrexate, and 5-fluorouracil pharmacokinetic data from one treatment would not be useful information from which the doses of subsequent courses could be determined.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias de la Mama/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Ciclofosfamida/farmacocinética , Femenino , Fluorouracilo/farmacocinética , Humanos , Metotrexato/farmacocinética , Persona de Mediana EdadRESUMEN
Angiotensin converting enzyme (ACE) has been measured in 102 biopsy-proven sarcoid patients, 70 patients diagnosed by clinical and radiological methods and 74 nonsarcoid patients as controls. The distributions of the various groups have been examined, and the effects of stage of disease, disease activity and prednisone treatment have been evaluated. Receiver operating characteristic (ROC) curves have been established for ACE, and the appropriateness of various statistical procedures is discussed. We have not discerned any effect of stage of sarcoidosis or of extent of disease activity on ACE values. The ROC curves suggest an upper limit of normal of about 50 U/L for our assay, and a sensitivity of 63% and specificity of 93%, yielding predictive values of 93% for a positive result and 74% for a negative result, with a likelihood ratio of 3.6. The results are discussed in the context of other work on ACE and in relation to the more invasive procedures of bronchoalveolar lavage and Gallium scan.
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Enfermedades Pulmonares/diagnóstico , Peptidil-Dipeptidasa A/sangre , Sarcoidosis/diagnóstico , Adulto , Anciano , Biopsia , Líquidos Corporales/análisis , Femenino , Humanos , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Sarcoidosis/sangre , Sarcoidosis/patología , Irrigación TerapéuticaRESUMEN
Serum angiotensin converting enzyme activity is increased in many patients with pulmonary sarcoidosis and has been proposed as a measure of disease activity. Assay of serum angiotensin converting enzyme, bronchoalveolar lavage, and gallium scans were performed in 27 patients with biopsy proved pulmonary sarcoidosis. There was a positive correlation between serum angiotensin converting enzyme activity and an index of pulmonary gallium uptake assessed by the National Institutes of Health method (r = 0.7, p less than 0.001). There was no significant relationship (r = 0.19) between serum angiotensin converting enzyme activity and bronchoalveolar lavage lymphocytes expressed as a proportion of cells recovered. Increase in the enzyme activity had a sensitivity of 50% as a means of detecting high intensity alveolitis but specificity was only 45%. There was no significant difference in mean angiotensin converting enzyme activity between the following groups: those with positive and those with negative gallium scans; those with bronchoalveolar lavage lymphocyte counts less than or equal to 28% and those with counts greater than 28%. Although there was a significant correlation between the enzyme activity and one component of the alveolitis of sarcoidosis, the data suggest that serum angiotensin converting enzyme activity alone is neither sensitive nor specific enough for high intensity alveolitis.
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Enfermedades Pulmonares/sangre , Peptidil-Dipeptidasa A/sangre , Sarcoidosis/sangre , Femenino , Humanos , Recuento de Leucocitos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/patología , Sarcoidosis/diagnóstico , Sarcoidosis/patología , Linfocitos T , Irrigación TerapéuticaRESUMEN
In a direct-measuring, sample-blank procedure for serum iron we obtained spuriously high results for renal hemodialysis patients. These spurious results were found to be the result of protein precipitating out of solution owing to anticoagulation of these patients with heparin during hemodialysis. Two methods are described for circumventing this interference: adjusting the pH of the buffer and adding sodium dodecyl sulfate (lauryl sulfate). We prefer the latter procedure for reasons which are discussed, and optimized conditions are described for it. The effects on results by this latter method of bilirubin, hemolysis, and turbidity are described. The method is also evaluated for precision and accuracy, and it is recommended for routine use. A significant "protein effect" (due to viscosity) is noted, which has implications for calibration of the American Monitor KDA instrument.