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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

[Serum human growth hormone assay. Comparison of six assay kits].

Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children.

Adolescent

Identifying severe aortic valvular stenosis by bedside examination.

Sixty-seven consecutive symptomatic patients with aortic valvular stenosis (AS) and no or slight aortic incompetence were prospectively examined bedside by a senior cardiologist before an invasive pre-operative investigation. A history of effort syncope had the highest predictive value (pos), 100%, for a significant degree of AS (defined as a calculated valve area less than or equal to 0.9 cm2 or a peak systolic pressure difference across the valve of greater than or equal to 40 mmHg). The absence of effort syncope had a predictive value (neg) of 40%. The corresponding figures for peak intensity of the murmur in mid-systole were 93 and 82%, respectively. For the combination of effort syncope and/or mid-systolic peak intensity of the murmur (borderline findings included) the predictive values were 90% (pos) and 94% (neg), respectively. No other combination of symptoms and physical finding was more discriminating. This combination of criteria for prediction of a significant stenosis was prospectively applied to the next 39 AS patients. The criteria were fulfilled by 29 patients and all were found to have a significant AS as were four of the 10 patients not fulfilling the criteria. These four falsely negative patients had a valve area/peak pressure difference of 0.5, 0.8, 0.8 cm2 and 43 mmHg. The inter-observer variation was studied in a third series by two senior cardiologists independently examining 22 AS patients. They were concordant in all with regard to a history of effort syncope and in all but one (0.6 cm2) with regard to the timing of the peak murmur. Bedside examination of an AS patient by an experienced cardiologist has a good predictivity for severity, and the inter-observer variation is low. Non-invasive laboratory investigations have only a supplementary role. However, as many patients have effort angina, a pre-operative invasive procedure including coronary arteriography is often unavoidable.

Adult

Circadian variation in ischemic threshold. A mechanism underlying the circadian variation in ischemic events.

BACKGROUND: There is a circadian pattern in the occurrence of cardiac events in patients with coronary artery disease. Whether changes in coronary vascular tone contribute to these phenomena is unknown. We measured the ischemic threshold, defined as either the heart rate or rate-pressure product at 1-mm ST segment depression during treadmill exercise and used it as an index of the lowest coronary vascular resistance; the premise was that when ischemic threshold became lower, coronary vascular resistance was higher, and vice versa. METHODS AND RESULTS: Fifteen patients (group A) with stable coronary artery disease underwent four identical treadmill exercise tests in 24 hours, and ischemic threshold was measured as the heart rate at the onset of 1-mm ST depression. Before each treadmill test, postischemic forearm vascular resistance was measured after 5 minutes of forearm occlusion, using strain-gauge plethysmography. Sixteen additional patients (group B) underwent two treadmill tests at 8 AM and 1 PM, and ischemic threshold was measured as the heart rate-blood pressure product at 1-mm ST depression. A circadian variation was noted: In group A, the heart rate-derived ischemic threshold was lower at 8 AM and 9 PM compared with noon and 5 PM (p less than 0.03). Also, in group B, the rate-pressure product-derived ischemic threshold was 8 +/- 2% lower at 8 AM compared with 1 PM (p = 0.008). A circadian variation parallel to the observed variation in ischemic threshold was also noted in the postischemic forearm blood flow, which was lower in the morning and at night (p less than 0.004). There was a strong correlation between postischemic forearm blood flow and ischemic threshold (p less than 0.0001), such that ischemic threshold was lower at the time of day when postischemic forearm blood flow was lower, and vice versa. CONCLUSIONS: A lower ischemic threshold in the morning suggests that the ischemia-induced coronary vascular resistance is increased at this time, a finding supported by a similar variation in postischemic forearm vascular resistance. Parallel changes in forearm and coronary resistance suggest that generalized (neural or humoral factors) rather than local factors are responsible for the observed circadian changes. Increased coronary tone in the mornings may not only contribute to the higher incidence of transient ischemia but may help trigger acute cardiac events at this time.

Aged

Follicular center cell lymphoma. Morphologic data relating to observer reproducibility.

Subjectivity and observer variation in non-Hodgkin's lymphoma continues to plague current classification schemes. It was thought important to assess objectively derived morphometric data to see if three categories of follicular center cell (FCC) lymphomas, follicular small cleaved cell, follicular mixed small cleaved and large cell, and diffuse and nodular large cell, actually fall into distinctly separate classes based on nuclear parameters. Mean nuclear area, contour index and invagination depth of neoplastic lymphocytes, and the percentage of invaginated and clefted nuclear profiles in each example of FCC lymphoma were evaluated by three different approaches. Results obtained from distribution of the morphometric data in scatter diagrams, calculation of the overlap index, and linear regression values, all revealed considerable (but variable) degrees of overlap between the three FCC subtypes regardless of the nuclear parameter employed. Where separation between FCC lymphomas was maximal, although still incomplete, there was no consistent correlation between the nuclear parameter and the pair of FCC lymphomas being compared. At least in terms of nuclear morphological features, non-Hodgkin's lymphomas of FCC type seem to represent a continuum of one disease process. The information provides a basis for understanding some reasons underlying the problem of observer variation in non-Hodgkin's lymphoma.

Cell Nucleus

Histological grading of prostatic carcinoma in prostatectomy specimens. Comparison of prognostic accuracy of five grading systems.

The prognostic accuracy of 5 histological grading systems (Broders, Anderson, Mostofi, Gleason and Mostofi-Schroeder) was compared. Grading was performed on 50 prostatectomy specimens by 5 pathologists. The results were averaged so as to reduce the impact of inter-observer variation. The Cox proportional hazards model was used to estimate the relationship between average grading scores and both time-to-recurrence and time-to-death by prostatic carcinoma. Age at surgery was considered to be a possible confounding factor and adjusted accordingly. The prognostic impact of the 5 grading systems (related to both recurrence and death caused by prostatic carcinoma) was judged by the likelihood ratio (LR) test score (chi 2 distributed with 1 df); for time-to-recurrence for the Mostofi-Schroeder score the LR was 6.54 and for the Gleason system it was 1.79. A stepwise procedure demonstrated that the best prognostic performance was reached with the Mostofi-Schroeder and Broders systems used together (with Mostofi-Schroeder weighted 1.5 times larger than Broders). For time-to-recurrence the median grading result was also used, giving results similar to the mean grading result. For time-to-death from prostatic carcinoma the LR test scores for all grading systems were relatively low. In this analysis the outcome of the Gleason system showed a minimum of prognostic ability, whereas the Broders and Mostofi-Schroeder systems had a reasonable predictive ability. Since the inter-observer variation of the Mostofi-Schroeder system was large, the Broders system is preferable. The restrictions and implications of this study are discussed and a brief review of the prognostic importance of grading of prostatic carcinoma is presented.

Aged

A procaryotic regulatory factor with a histone H1-like carboxy-terminal domain: clonal variation of repeats within algP, a gene involved in regulation of mucoidy in Pseudomonas aeruginosa.

A novel procaryotic transcriptional regulatory element, AlgP, with a histone H1-like carboxy-terminal domain was identified in Pseudomonas aeruginosa. AlgP is required for transcription of the key biosynthetic gene algD, which is necessary for production of the exopolysaccharide alginate causing mucoidy in P. aeruginosa. Mucoidy is a critical virulence determinant of P. aeruginosa invariably associated with the respiratory infections causing high mortality in cystic fibrosis. Here we show that AlgP and histones H1 both have repeated units of the Lys-Pro-Ala-Ala motif (KPAA) and its variations within their long (over 100 amino acids) carboxy-terminal domains. This region of histone H1 tails has been shown to bind to the linker DNA in eucaryotic chromatin fibers. A synthetic 50-mer peptide consisting of repeats from the AlgP carboxy-terminal domain was found to bind DNA in a mobility shift DNA-binding assay. AlgP is encoded by a gene that contains multiple direct repeats organized as tandem, head-to-tail, 12-base-pair (bp) units overlapping with six highly conserved 75-bp units. The repetitive structure of the algP gene appears to participate in the processes underlying the metastable character of mucoidy in P. aeruginosa. Relatively large DNA rearrangements spanning the region with tandem direct repeats encoding the carboxy-terminal histone H1-like structure of AlgP were detected in several strains upon conversion from the mucoid to the nonmucoid phenotype. The frequency of the detectable algP rearrangements associated with the transition into the nonmucoid state varied from strain to strain and ranged from 0 to 50%. The nonmucoid derivatives with the clearly rearranged chromosomal copy of algP were complemented to mucoidy with plasmids containing algP from P. aeruginosa PAO. When a random collection of mucoid strains, isolated from different cystic fibrosis patients, was analyzed by using polymerase chain reaction, an additional level of strain-dependent sequence variation in algP was observed. Variations in the number of the 12-bp repeats were found; however, they did not appear to influence the mucoid status of the strains examined. Thus, the repeated region of algP appears to be a hot spot for DNA rearrangements and strain-dependent variability.

Amino Acid Sequence

Comparative analysis of chloroplast genomes in ten holly (Ilex) species: insights into phylogenetics and genome evolution.

In order to clarify the chloroplast genomes and structural features of ten Ilex species and provide insights into the phylogeny and genome evolution of the genus Ilex, we conducted a comparative analysis of chloroplast genomes using bioinformatics methods. The chloroplast genomes of ten Ilex species were obtained, and their structural features and variations were compared. The results indicated that all chloroplast genomes in the genus Ilex exhibit a double-stranded circular structure, with sizes ranging from 157,356 to 158,018&#xa0;bp, showing minimal differences in size. The chloroplast genomes of the ten Ilex species have a relatively conservative gene count, with a total of 134 to 135 genes, including 88 or 89 protein-coding genes, and a conserved number of 8 rRNA genes. Each chloroplast genome contains 3 to 123 SSR (Simple Sequence Repeat) sites, predominantly composed of mononucleotide and trinucleotide repeats, with no detection of pentanucleotide or hexanucleotide repeats. The variation in dispersed repeat sequences among Ilex species is minimal, with a total repeat sequence number ranging from 1 to 14, concentrated in the length range of 30 to 42 base pairs. The expansion and contraction of chloroplast genome boundaries among Ilex species are relatively stable, with only minor variations observed in individual species. Variations in non-coding regions are more pronounced than those in coding regions, with the variability in the Large Single Copy region (LSC) being the highest, while the variability in the Inverted Repeat region A (IRa) is the lowest. The divergence time among Ilex species was estimated using the MCMC-tree module, revealing the evolutionary relationships among these species, their common ancestors, and their differentiation throughout the evolutionary process. The research findings provide a valuable reference for the systematic study and molecular marker development of Ilex plants.

Genome, Chloroplast

Variability of arterial blood gas values in stable patients in the ICU.

To establish guidelines for the interpretation of changes in arterial blood gas (ABG) values, we studied 29 clinically stable ICU patients for spontaneous variability in PaO2, PaCO2 and pH. ABGs were sampled six times over a 50-minute period, during which all patients received a fixed FIO2 of 0.5 via endotracheal tube and underwent no therapeutic interventions. Each sample was analyzed in duplicate with careful attention to method of collection and measurement. The range separating the lowest and highest PaO2 varied from 1 to 45 mm Hg (16.2 +/- 10.9 mm Hg [mean +/- SD] ). For PaCO2 this range was from 1 to 8 mm Hg (3.0 +/- 1.9 mm Hg). Coefficient of variation for PaO2 and PaCO2 averaged 5.1 +/- 3.2 percent (mean +/- SD) and 3.0 +/- 1.5 percent respectively. pH varied within 0.03 +/- 0.02 units. Percentage change in PaO2 between sequential intrapatient samples averaged 5.3 +/- 2.8 percent (mean +/- SD) and 7.1 +/- 7.9 percent over ten- and 50-minute intervals, respectively. Various clinical features were analyzed by multiple regression analysis for their relation to PaO2 variation. Only leukocyte count and mean arterial oxygen content were statistically significant associations (p less than 0.05), but together explained less than 35 percent of the variation observed. Because considerable spontaneous variation occurs, even in stable patients, clinicians should base therapeutic decisions on trends in PaO2 values rather than on isolated changes interpreted without appropriate clinical correlation.

Adult

Using replicate observations in observer agreement studies with binary assessments.

By introducing replicate observations into observer agreement studies, one can obtain better measures of observer agreement than heretofore possible. New methodology based on the analysis of latent variables allows a separation of within- and between-observer variation for binary measures of assessment among pairs of observers. Maximum likelihood estimation and hypothesis testing are discussed. The methodology is illustrated using data on the assessment of dysplasia by pathologists.

Biometry