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Some observations on variations in filament overlap in tetanized muscle fibres and fibres stretched during a tetanus, detected in the electron microscope after rapid fixation.

Anomalous tension development which would not be predicted from the descending limb of the length-tension curve occurs during prolonged tetani and after stretch during a tetanus. Variations in filament overlap might account for all or part of the tension enhancement. Fibres isolated from frog skeletal muscle were rapidly fixed during a tetanus with mercuric chloride in ethanol and chloroform so that the correct alignment of the filaments in the overlap zones was preserved. The fibres were examined in polarized light with compensation, and in the electron microscope. There were variations in striation spacing along the length of the fibres, and severe shortening with contraction bands near the tendon insertions, confirming observations made by others on live fibres. Many variations in filament overlap which would not be detectable by light microscopy or laser diffraction were seen in the electron microscope. In a pilot study we measured differences in the width of the overlap zones between half-sarcomeres in a small area and within individual half-sarcomeres. In the latter case the variations were greater in a fibre which developed creep of tension and one which did not. Even greater variations were seen in three fibres stretched during a tetanus, and, in two of these, there were some grossly elongated half-sarcomeres in which the filaments had pulled out of the overlap zones, leaving gaps.

Animals

Inter-observer agreement and clinical diagnosis of leprosy for prophylaxis studies.

Clinical diagnosis is still the most useful tool for detecting early cases of leprosy in field research. In prophylaxis studies accuracy of clinical diagnosis of leprosy is important during intake as well as for measuring efficacy of the intervention. This paper reports our observations regarding the extent of inter-observer variations in clinical diagnosis of leprosy and its implications for a prophylaxis study. Information on 225 suspects and cases of leprosy, each examined independently by three senior workers after initial standardization, was used for this purpose. Agreement among the examiners regarding the presence of skin patch, thickened nerve trunk and sensory deficit was fairly high (Kappa = 0.7). Agreement on the presence of infiltration in a skin patch was not satisfactory (Kappa = 0.4-0.5). It was observed that in clinical diagnosis of leprosy, presence of skin patch and sensory deficit, as well as thickened nerve trunk and related anaesthesia were correlated observations. The influence of inter-observer variations on defining leprosy problem in the community can be quite large. The paper suggests some ways of overcoming the problem.

Adult

Pitfalls in the diagnosis of recurrent ulceration after surgery for peptic ulcer disease.

We have studied the accuracy of diagnostic methods in achieving a diagnosis in 75 patients with 81 proven episodes of recurrent ulceration. When the endoscopic findings did not permit an accurate diagnosis, radiology usually provided no additional information. The sensitivity of a combined diagnostic approach was not different from that of endoscopy alone, and so the routine use of upper GI radiographs in addition to endoscopy should, therefore, be abandoned. We also assessed observer variation among endoscopists prospectively in 38 patients investigated for dyspepsia after operation for peptic ulcer. Major observer variation in diagnosing suspected recurrent ulceration occurred in 11% of patients, with a sensitivity and specificity higher than 77 and 94%, respectively. As not all the postoperative gastroduodenojejunal mucosal breaches are peptic, we suggest that acid output and enterogastric reflux assessments are useful diagnostic adjuncts to endoscopy.

Deglutition Disorders

Systematic oserver variation in trachoma studies.

There has been increasing awareness in recent years among trachomatologists, as well as among workers in other fields of medical research, of the frequency and importance of observer variation in epidemiological studies and clinical trials. In trachoma, the lack of simple definitive laboratory diagnostic procedures suitable for wide application has placed the onus largely, and usually exclusively, on clinical observation.The study reported is based on the recorded observations of two skilled ophthalmologists in an epidemiological survey covering more than 35 000 persons in Taiwan. Observer differences were found to lie not only in deciding whether a case is trachomatous or not but also in assigning cases diagnosed as trachoma to the appropriate evolutive stage of the WHO trachoma classification.THE CONCLUSIONS REACHED ARE THAT: (a) inter- and intra-observer variations of some degree are inevitable if dependence is placed on clinical examination alone; (b) it is possible by preliminary testing of observers' interpretation of clinical signs to determine the nature of these differences, to assess their importance, and to reduce them; also to set base-lines for the detection of subsequent divergences over time; and (c) it is better to have two observers than one in any trachoma survey or clinical trial.

Adolescent

Observer bias in blood pressure studies.

Observer variation in blood pressure measurement following training with standard techniques has been investigated in a study of 7735 middle-aged men. The initial training produced consistent results between observers, but there were progressive deteriorations in the ensuing months. Subsequent re-training led to marked though inconsistent reductions in variation, but within 1 or 2 months, observers reverted back to an individual level of bias. The magnitude of observer variation is in line with the few other published accounts, and is sufficient to have important implications for group comparisons, clinical trials, and the clinical care of individual patients. Four methods of reducing observer variation are considered: regular re-training, self-measurement and ambulatory monitoring, automatic sphygmomanometers, and adjustment in the analysis. The adjustment procedure used in the British Regional Heart Study is described. Regular and frequent re-training with monitoring of performance, or the use of automatic machines are presently considered the two most practical methods of reducing observer variation.

Adult

Blood P50 calculated from a single measurement of pH, PO2, and SO2.

P50 was calculated from a single measurement of pH, Po2, and So2 at a known temperature in 135 blood samples from 21 normal nonsmokers and eight patients. In the 92 blood samples with So2 between 20 and 90 per cent, the standard deviation of repeated calculated P50's on the same sample of blood at different So2 was plus or minus 1.0 Torr. Below So2 of 20 per cent and above So2 of 90 per cent, the standard deviations were plus or minus 5.5 and plus or minus 2.4 Torr, respectively. Combined measurement errors of plus or minus 1 Torr in Po2, plus or minus 1 percent in So2, plus or minus 0.01 in pH, and plus or minus 0.1 degree C in temperature are sufficient to explain the observed variation in calculated P50 in 90 per cent of 135 blood samples from 29 subjects and account for the greater observed variation at So2 less than 20 per cent and greater than 90 per cent.

Carbon Dioxide

Clinical assessment of disease activity in rheumatoid arthritis.

A new experimental design was developed to study the value of clinical parameters of disease activity in patients with rheumatoid arthritis. Ten patients with classical rheumatoid arthritis were examined by five senior doctors in a department of medical rheumatology. In spite of an attempt to make the clinical examination as uniform as possible the inter-observer variation among the doctors was greater than the variation among the patients, for the following parameters: joint pain at rest, joint tenderness and joint swelling. An acceptable inter-observer variation in relation to patient variation was found for 1) a combined registration of joint pain at rest or on movement, 2) duration of morning stiffness, 3) grip strength, 4) subjective well-being as indicated on a visual analogue scale, 5) fingertip--palm distance, and 6) maximum flexion-extension in elbows, wrists and knees. The variation from morning to afternoon and from day to day was negligible. It is concluded that registration of elaborated articular scores is useless in the daily routine in rheumatological departments when different doctors examine the patients.

Adult

Comparison of egg excretion and serum pepsinogen levels as measures of nematode worm burdens in calves with limited pasture exposure.

Four- to 6-mo-old calves raised on clean pastures were allowed to graze for about 30 days on pastures naturally contaminated with Ostertagia ostertagi, Cooperia spp., Haemonchus placei, and Nematodirus helvetianus. The calves were then housed on concrete for 3 wk before slaughter. At necropsy the eggs per gram of feces (EPG) and the total worm burdens from the abomasum and small intestine were determined. Blood samples were also obtained for serum pepsinogen (PEP) assays. A total of 44 calves was sampled over 27 mo. Adult worm totals were distributed more normally after logarithmic transformation (LOGTOTAL), and EPG and PEP were distributed more normally after square root transformation (SQRT--EPG; SQRT--PEP). Correlation between LOGTOTAL and either SQRT--EPG or SQRT--PEP was about 0.7. These correlations were higher than those obtained with nontransformed data, suggesting that either EPG or PEP are easily measured variables that explain a significant amount of the variation observed in total worm burdens. Polynomial regression models of a cubic order using the SQRT--EPG accounted for 78% of the variation observed in the LOGTOTAL, whereas SQRT--PEP accounted for 58% of the variance. Within the range of worm burdens observed, these results indicate that EPG has value in estimating total worm burdens of naturally infected calves, and that pepsinogen levels are of less value for analysis of total worm burden in calves with a limited previous exposure to trichostrongyle nematodes.

Abomasum

Variations in histopathological evaluation of non-neoplastic colonic mucosal abnormalities; assessment and clinical significance.

The variation between three pathologists examining histological features seen in non-neoplastic colonic mucosa from 40 biopsies was analysed. Several procedures to express observer variation were used and compared, with emphasis on kappa statistics. Only five features, the presence of ulceration, villous surface, epithelioid granulomas, severe mucus depletion and crypt abscesses were sufficiently reproducible by the three pairs of pathologists. These findings suggest that other criteria used for the classification of inflammatory bowel disease are potentially unsatisfactory. When results from different studies on biopsies are being compared, influence of observer variation should be identified. Comparison of statistical techniques showed overall variation to be less useful than other statistical procedures. There was little difference between results from kappa statistics and other measures of agreement (overall agreement excluded).

Biopsy

Role of uptake in gamma-aminobutyric acid (GABA)-mediated responses in guinea pig hippocampal neurons.

Intracellular recordings were obtained from hippocampal pyramidal neurons maintained in vitro. Measurements were made of the conductance change induced by iontophoretically applied gamma-aminobutyric acid (GABA) and, using voltage-clamp techniques, of inhibitory postsynaptic currents resulting from activation of inhibitory pathways. Analysis of GABA iontophoretic charge-response curves indicated that there was considerable variation among neurons with respect to the slope of this relation. The placement of the GABA-containing pipette did not appear to be responsible for the observed variation, since vertical repositioning of the pipette did not alter the slope of the charge-response relationship. Steady iontophoresis of GABA from one barrel of a double-barreled pipette markedly affected the charge-response relation obtained when short pulses were applied to the other barrel. The curve was shifted to the left, and the slope was decreased. Concomitantly, the enhanced GABA-induced responses were prolonged. Similar alterations in GABA responsiveness were observed when the uptake blocker, nipecotic acid, was iontophoretically applied. Furthermore, bath application of saline containing a reduced sodium concentration (25% of control) also produced a prolongation of GABA-mediated responses. Under voltage clamp, inhibitory postsynaptic currents were observed to have biphasic decays. The initial, fast decay was prolonged by an average of 18% by nipecotic acid, whereas the later, slow phase was prolonged by 23%. The results of these studies support the hypothesis that a saturable GABA uptake system is responsible for the observed variation in the charge-response curves and, in turn, underlies the apparent sensitizing effect of excess GABA application. The results also suggest that a reduction of transmitter uptake affects the time course of inhibitory postsynaptic currents in the hippocampus.

Animals

Precision of dual photon absorptiometry measurements: comparison of three different methods of selection of the region of interest.

To determine the short-term reproducibility of bone mass calculations with dual photon absorptiometry of the lumbar spine (L2-L4), duplicate measurements in healthy subjects were used. Three different methods for selection of region of interest were compared: a rectangular region with variable height and width, an irregular region to be drawn freely by the operator and the standard calculation software supplied with the bone densitometer. Contributions of changes in size and location of the region of interest on calculated bone mineral mass were also investigated. An increase in height of the region by 2 scan lines caused an increase in bone mineral content (BMC) of 8.4% +/- 1.8%. Enlargement in width by 2 pixels in each scan line caused an increase in BMC of 2.5% +/- 1.3%. The difference between these region of interest changes was significant (P less than 0.0005). The use of a rectangular region, optimized to enclose L2-L4 in each person but of the same size in both measurements, resulted in a reproducibility of 1.4% and 0.7% respectively for 2 observers, with an inter observer variation of 1.2%. The reproducibility of the duplicate measurements was worse for the other methods of region of interest selection. A further series of duplicate DPA measurements in normal subjects, but with a standard meal between the measurements, showed a larger variation in the results. Again the reproducibility of the calculations using the rectangular region was better than with the other methods, with much less inter observer variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Assessment of bone mineral content and bone mass by non-invasive radiologic methods.

Methods for quantitative determination of bone mineral and bone mass in normal subjects and in patients with metabolic bone disorders can be measured by the Compton scattering technique, the neutron activation analysis, by measurement of metacarpal bone mass, by single and dual photon absorptiometry, and by quantitative computed tomography. Measurement on metacarpal bone (radiogrammetry) seems to be able to distinguish between resorption and/or new bone formation at the periosteal and/or endosteal surface. The intraindividual observer variation on combined cortical thickness (D-d), cortical area (D2-d2), metacarpal bone mass (D2-d2)/D2-varies from 0.7 to 2.5 per cent and the interindividual observer variation from 1.0 to 5.8 per cent. Single photon absorptiometry measures bone mineral content in the forearm with great precision. The reproducibility using repeated measurements and automatic selection of the measuring area is about one per cent and can be used to follow changes in mineral content with time in patients with metabolic bone diseases. The dual photon absorptiometry may be used for measurements of bone mineral content in lumbar spine, in the femoral neck and measurement of total body calcium with an accuracy of less than 6 per cent and a precision below 3 per cent. Quantitative computed tomography has the ability to measure trabecular and cortical bone both centrally and peripherally. Using CT scanning, scanner related changes with time (day-to-day variation +/- 4%), patient repositioning (less than 1.5%), and fat concentration (residual uncertainty of approximately 1/6 of the biologic variation) are important factors influencing the accuracy and reproducibility of the values of the measured bone mineral content.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Diseases, Metabolic

The effects of blood flow and detoxification on in vivo cholinesterase inhibition by soman in rats.

The in vivo time course of cholinesterase inhibition was measured in brain, lung, spleen, hind limb skeletal muscle, diaphragm, intestine, kidney, heart, liver, and plasma of rats receiving 90 micrograms/kg soman, im. This dose of soman produced severe respiratory depression and transient hypertension, but no significant changes in the cardiac output or heart rate of anesthetized rats. The rate and maximal extent of in vivo cholinesterase inhibition by soman varied widely among the tissues. Although cardiac output was unchanged by soman administration, the blood flow in heart, brain, and lung (bronchial arterial flow and arteriovenous shunts) was increased, whereas blood flow in spleen, kidney, and skeletal muscle was decreased. The relative importance of tissue blood flow, tissue levels of cholinesterase and acetylcholinesterase, and tissue levels of soman-detoxifying enzymes (diisopropyl-fluorophosphatase and carboxylesterase) in determining the in vivo rate and maximal extent of cholinesterase inhibition was examined by multiple regression analysis. The best multiple regression model for the maximal extent of cholinesterase inhibition could explain only 63% of the observed variation. The best multiple regression model for the in vivo rate of cholinesterase inhibition contained three independent variables (blood flow, carboxylesterase, and cholinesterase) and could account for 94% of the observed variation. Of these three variables blood flow was the most important, accounting for 79% of the variation in the in vivo rate of cholinesterase inhibition. This suggests that it may be possible to use a flow-limited physiological pharmacokinetic model to describe the kinetics of in vivo cholinesterase inhibition by soman.

Acetylcholinesterase

Brief report: parainfluenza virus type 3 infections: findings in Sydney and some observations on variations in seasonality world-wide.

Parainfluenza virus type 3 (Para 3) is an important childhood pathogen causing a significant amount of bronchiolitis and pneumonia in infants. Virus data were analysed over a twelve-year period (1978-1989), and a peak incidence of infection was observed in spring as in Houston, USA, unlike in the United Kingdom where summer epidemics appear to be the norm. The temperature ranges were analysed in the different study areas during Para 3 epidemics and similar ranges in temperature were noted which might provide an explanation for the apparently discordant findings in seasonality reported from different parts of the world.

Australia

Assessment of follicular development in clomiphene induced cycles by means of ultrasound and laparoscopy: a comparative study.

Fifty clomiphene/H.C.G. stimulated patients undergoing laparoscopy as part of their infertility work up consented to participate in a study on: the reproducibility of ultrasonic measurement of follicular size as expressed by the inter and intra observer variation; the accuracy of ultrasonic assessment of location, number and size of follicles and the growth rate of the Graafian follicle during the last 12 hr prior to oocyte collection. The inter and intra observer variation was moderate to good. Correct diagnosis of the dominant follicle was made in 73%, of the number of follicles in 72% and of follicular size (difference in size between ultrasound and laparoscopy less than 2 mm) in 48% of the material studied. There was a rather wide range in follicular growth rate values during the last 10-17 hr prior to laparoscopy.

Chorionic Gonadotropin

The quality and relevance of peripheral neuropathy data on a diabetic clinical information system.

Routinely collected peripheral neuropathy data entered on a diabetic clinical information system since 1979 have been audited for completeness, consistency, accuracy (inter-observer variation), validity by comparison with biothesiometry, and relevance by life table analysis for foot ulceration. Peripheral neuropathy was defined by a neuropathy disability score > or = 4. The data were 98% complete. Forty-nine of 3405 (1.4%) had inconsistent records. Agreement between observers for clinical examination was significant (p < 0.05) for aggregate neuropathy score and its individual components except the knee jerk: Kappa score for observer variation for neuropathy score 0.56 (95% confidence interval 0.36-0.76). There was good agreement between neuropathy defined as aggregate score > or = 4, and as combined vibration perception thresholds for both feet > 60 V: Kappa statistic 0.62 (95% confidence interval 0.44-0.80). The chance of developing a foot problem in 3 years increased from 3% for patients with a score of zero to 45% for people with a score of between 9 and 12. We conclude that the calculation of a clinical neuropathy score is a simple, valid and relevant method for diabetes care both in hospital and the community. When combined with palpation of peripheral pulses most patients at risk of foot ulceration can be identified allowing targeting of preventive chiropody and orthotic resources.

Diabetic Neuropathies

Observer performance in assessment of condylar position in temporomandibular joint radiograms.

The condylar position at centric occlusion has been considered important in diagnosis of the temporomandibular joint. The present study describes inter- and intra-observer variation in radiographic assessment of condylar position. One radiogram obtained by using an individualized lateral oblique transcranial projection and three corrected sagittal tomograms from the lateral, central, and medial parts of the joint were selected from each of 31 patients. In the resulting 124 radiograms three observers assessed the position of the condyle as posterior, central, or anterior on two occasions, 3 months apart. Concordant reports for all three observers were found in 63%. The interobserver agreement two by two ranged between 69% and 79%, whereas the intraobserver agreement ranged between 81% and 90%. The observer variation and limitations of radiographic techniques should be considered when the therapeutic implication of condylar position is discussed.

Dental Occlusion, Centric

Expected genetic drift and observed gene variation in a small isolated human population.

Data on the gene frequencies of four blood groups and six polymorphic erythrocyte enzymes were collected in a small population of the Northern Apennines (municipality of Zeri, Tuscany, Italy), whose civic records are available from 1866 on. Starting from the assumption that the mean gene frequencies of large populations of the neighbouring regions may represent a good estimate of the frequencies of the 'mother population' of the isolate, an observed value of the standardized ('Wahlund') variance of gene frequencies was computed and found to be 0.0131. The expected value of the same variance, due to random drift, has been computed on the basis of an evaluation of the immigration to the isolate, drawn from the marriage register of the municipality: this value was 0.0103.

Emigration and Immigration