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Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy.

OBJECTIVE: Chronic diarrhea is a relatively common condition with multiple diverse etiologies. Stool testing may serve as a diagnostic aid to discriminate the presence or absence of organic pathology, such as colorectal inflammation. Calprotectin (a leukocyte-derived protein) and hemoglobin can be measured quantitatively from stool and represent candidate inflammation biomarkers. The aim of this study was to assess and compare the screening performance of fecal calprotectin and fecal hemoglobin among colonoscopy referral patients with chronic diarrhea of unknown origin or chronic colitis of unknown activity. METHODS: All subjects were identified prospectively and each submitted a single stool sample before purgation. Fecal calprotectin (PhiCal; Nycomed Pharma, Oslo, Norway) and fecal hemoglobin (HemoQuant; Mayo Medical Laboratories, Rochester, MN) assays were performed in separate laboratories by masked technicians. Colonoscopic and histological findings served as criterion standards for establishing the presence or absence of colorectal inflammation. RESULTS: Among 110 subjects who provided complete fecal assay data, 29 (26%) had and 81 (74%) did not have colorectal inflammation. Increased fecal calprotectin levels were significantly (p = 0.0001) associated with the presence of colorectal inflammation, whereas fecal hemoglobin levels were not (p = 0.61). Direct comparison of the fecal assays revealed that calprotectin was a more sensitive biomarker for colorectal inflammation at all specificity levels (p = 0.0001). CONCLUSIONS: In this study of colonoscopy referral patients, colorectal inflammation was reflected by fecal calprotectin but not by fecal hemoglobin levels. Assay of fecal calprotectin holds promise as a triage tool to identify inflammatory causes of chronic diarrhea.

Adolescent↗

Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia.

OBJECTIVES: Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to fecal hemoglobin (Hb) and colonoscopy as the existing criterion standards for stool screening and structural evaluation, respectively. METHODS: Subjects included colonoscopy patients with a personal history of colorectal neoplasia, family history of colorectal cancer, or iron deficiency anemia. Stool specimens were collected before purgation, processed appropriately, and quantitatively analyzed for calprotectin (Nycomed Pharma, Oslo, Norway) and for Hb (Mayo Medical Laboratories, Rochester, MN) by masked technicians. Colonoscopies were performed by experienced endoscopists without prior knowledge of the fecal assay results. RESULTS: Among 412 subjects, 97 (24%) subjects had one or more colorectal neoplasms (including three with adenocarcinomas). Fecal calprotectin levels did not differ significantly between subjects with versus subjects without colorectal neoplasms (p = 0.33). Neither tumor number (p = 0.85) nor tumor size (p = 0.86) significantly influenced the observed fecal calprotectin concentrations. Estimates of the sensitivity, specificity, and positive and negative predictive values of fecal calprotectin for any colorectal neoplasms were 37%, 63%, 23%, and 76%, respectively. Comparable performance estimates for fecal Hb were 3%, 97%, 27%, and 77%, respectively. CONCLUSIONS: In this cohort of colonoscopy patients at above average risk, fecal calprotectin was a poor screening biomarker for colorectal neoplasia. Further investigation of tumor-derived, rather than blood-based, biomarkers may be a more rewarding approach to stool screening for colorectal neoplasia.

Aged↗

Influence of the pineal gland and circadian rhythms in circulating levels of thyroid hormones of male hamsters.

Thyroxin (T4) and triiodothyronine (T3) were measured by radioimmunoassay in serum of hamsters sacrificed at 4-hr intervals throughout the daily light-dark cycle (14L/10D). Both T4 and T3 concentrations increased significantly during the L period of the daily cycle and decreased during the D period of the cycle; A.M. versus P.M. differences in free thyroxin indices (FTI) were also studied using the T4 and T3 uptake assays of Nuclear Medical Laboratories (Dallas, Texas). The free thyroxin index was significantly greater in serum samples of hamsters sacrificed at 7 P.M. than at 7 A.M. (lights on at 6:30 A.M.). Serum taken at 7 P.M. had less unsaturated binding sites than serum taken at 7 A.M. No significant A.M. versus P.M. differences in free thyroxin index were found in blind hamsters, although blind hamsters had significantly lower T4 and FTI than controls. Placing melatonin in the drinking water at a dose of 80 micrograms/ml did not significantly influence hormone levels. The greatest difference in hormone concentrations between control and blinded hamsters was found in P.M. samples. Blind hamsters had FTIs that were 48% of P.M. controls. Pinealectomy prevented the effects of blinding on T4 levels and FTIs.

Animals↗

Determination of bromine in blood serum by 125I excited x-ray fluorescence.

A radioisotope excited XRF method based on the use of five 10-mCi 125I point sources arranged in a newly designed configuration is applied to the bromine determination in very small blood serum samples (less than or equal to 50 microL). The possibility of determination of 0.05 micrograms Br in blood serum during 100 s counting time with a standard deviation of +/- 10% is described. The simplicity and low cost of the present method are major advantages over the other nondestructive methods and render it suitable for medical laboratories.

Bromine↗

Dosimetric aspects of the therapeutic photon beams from a dual-energy linear accelerator.

Parameters of the photon beams (6 and 20 MV) from a dual-energy linear accelerator (Mevatron-KD, Siemens Medical Laboratories, CA) are presented. The depth dose characteristics of the photon beams are dmax of 1.8 and 3.8 cm and percentage depth dose of 68% and 80% at 10-cm depth and 100-cm source-surface distance for a field size of 10 X 10 cm2 for 6 and 20 MV, respectively. The 6 and 20 MV beams were found to correspond to nominal accelerating potentials of 4.7 and 17 MV, respectively. The stability of output is within +/- 1% and flatness and symmetry are within +/- 3%. These figures compare favorably with the manufacturer's specifications.

Humans↗

Evolving approaches to management of quality in clinical microbiology.

Quality management in clinical microbiology began in the 1960s. Both government and professional societies introduced programs for proficiency testing and laboratory inspection and accreditation. Many laboratory scientists and pathologists were independently active and creative in expanding efforts to monitor and improve practices. The initial emphasis was placed on intralaboratory process. Later, attention was shifted to physician ordering, specimen collection, reporting, and use of information. Quality management in the laboratory depends in large part on the monitoring of indicators that provide some evidence of how laboratory resources are being used and how the information benefits patient care. Continuous quality improvement should be introduced. This consists of a more thorough assessment of doing the right things versus the wrong things in terms of customer demand and satisfaction and studying the cumulative effect of error when responsibility is passed from one person to another. Prevention of error is accomplished more through effective training and continuing education than through surveillance. Also, this system will force more conscious attention to meeting the expectations of the many customers that must be satisfied by laboratory services, including patients, physicians, third-party payers, and managed-care organizations.

Clinical Competence↗

Spurious sulfamethoxazole-trimethoprim resistance of Salmonella typhi.

Several studies have identified thymidine excess in susceptibility test media as the cause of spurious resistance of various bacteria to sulfamethoxazole-trimethoprim. We document the phenomenon in Salmonella typhi and Salmonella paratyphi-A and demonstrate its occurrence in 3 of 17 (18%) lots of Mueller-Hinton agars now in use in major medical laboratories in Lima, Peru. The findings are particularly significant because sulfamethoxazole-trimethoprim is an important alternative to chloramphenicol or ampicillin for the treatment of typhoid and paratyphoid fevers.

Anti-Bacterial Agents↗

Contrast of survey results between state and a cohort of nonstate mycobacteriology laboratories: changes in laboratory practices.

Based on the recommendations of a 1992 conference on tuberculosis, the Centers for Disease Control and Prevention (CDC) established programs for upgrading mycobacteriology laboratories by providing them with monies and focused training. In 1991, state public health laboratories were surveyed to determine the methods they were using for primary Mycobacterium tuberculosis testing and their turnaround times for reporting testing results. A similar survey of nonstate laboratories participating in the National Laboratory Training Network-sponsored, M. tuberculosis-focused training programs was conducted from May 1992 to June 1993. In 1994, follow-up surveys of both the state- and nonstate-laboratory cohorts were conducted with the questionnaire from the initial survey plus additional questions that asked about interventions and changes occurring in the laboratory since the original survey. Although both cohorts showed increases in the percentages of laboratories meeting the recommended turnaround times for reporting M. tuberculosis testing results and using the recommended rapid methods for testing, generally, the increases made by the state laboratories were greater. By June 1994, all state laboratories were using a rapid method for M. tuberculosis isolate identification compared with 88% of the nonstate laboratories. The percentage of laboratories identifying isolates within the recommended 21 days also increased more in the group of state laboratories than in the group of nonstate laboratories (state laboratories, 22 to 73%; nonstate laboratories, 55 to 59%). Responses from the follow-up survey showed large differences in the percentages of laboratories that received CDC funding (state laboratories, 100%; nonstate laboratories, 6%) and participated in M. tuberculosis training (state laboratories, 98%; nonstate laboratories, 45%). These results indicate that adequate funding and focused training are critical in maintaining state-of-the-art mycobacteriology laboratories.

Bacterial Typing Techniques↗

Nine cases of accidental exposure to dimethyl sulphate--a potential chemical weapon.

Dimethyl sulphate (DMS) is an innocuous appearing, widely used, and highly toxic chemical. It is used both as a methylating agent in industrial chemical synthesis and in medical laboratories for chemical cleavage of DNA. It is readily absorbed through the skin, mucous membranes, and gastrointestinal tract. Delayed toxicity allows potentially fatal exposures to occur prior to development of any warning symptoms. Toxicity is manifested initially by mucosal inflammation of eyes, nose, oropharynx, and airways. This can progress to severe airway oedema and necrosis, and non-cardiogenic pulmonary oedema. Other systemic effects include convulsions, delirium, coma, and renal, hepatic, and cardiac failure. All these features make DMS a potential chemical weapon. We report nine cases of varying degrees of inhalational exposure to DMS, occurring as a result of a single chemical spillage incident in the United Kingdom. Industrial poisoning is surprisingly rare and there are few previous reports in the literature outside China.

Accidents, Occupational↗

Histopathology and the future.

A plea is made for a revolution in diagnostic histopathology. In the present account a brief analysis is given of the drawbacks to existing methods used in the histopathological laboratory and suggestions are made for research in those methods which could lead to progress in the speed and sensitivity of diagnosis and to great economies in histopathological practice. The abolition or replacement of certain techniques used at present is proposed.

Clinical Laboratory Techniques↗

Introduction of a Vickers M300 analyser into the routine service of a hospital laboratory. 1. Installation, staffing, logistics.

A Vickers M300 analyser has been successfully installed in a busy hospital laboratory. A permanent team of operators is used, but this introduces problems for staff rotation, particularly for educational purposes. The vials used for the collection of samples are an essential feature of the system, but they present many difficulties and are no longer used for collecting samples from outpatients, or at remote sites. Direct costs during 1974, excluding staff and depreciation, amounted to approximately pounds 0-45 per patient sample: this is assessed on the rising workload during implementation. An increased workload could still be handled with existing staff. The siting of such high-capacity analysers constitutes an important policy decision.

Autoanalysis↗

National Health Service laboratories in England, 1966-74.

Laboratory workloads increased substantially between 1966 and 1974, the total number of laboratories was reduced, and productivity improved. The trends are likely to continue, but in the present economic situation the availability of accommodation will be an important constraint in determining the pattern of future development.

England↗

Cost effectiveness of routine postmortem histology.

In a retrospective study of the records of 160 necropsies it was found that, according to the clinical and gross necropsy findings, no clinically important abnormality would have been anticipated in 46% of the tissue samples. The estimated annual cost of processing this material alone was pounds 10,500, including the salary of one full time medical laboratory scientific officer (MLSO). Few of the microscopic findings led to a change in diagnosis. It is suggested that unselected postmortem histology is, for diagnostic purposes, not cost effective.

Autopsy↗