Associations between trilobite intraspecific moulting variability and body proportions: Estaingia bilobata from the Cambrian Emu Bay Shale,Australia

Trilobites were notably flexible in the moulting behaviours they employed, producing a variety of moult configurations preserved in the fossil record. Investigations seeking to explain this moulting variability and its potential impacts are few, despite abundant material being available for study. We present the first quantitative study on moulting in a single trilobite species using a dataset of almost 500 moult specimens of Estaingia bilobata from the Cambrian (Series 2, Stage 4) Emu Bay Shale, South Australia. Specimens were categorized by moulting mode (Salter's or Sutural Gape) and their associated configurations, and their body proportions measured from both a museum collection (including a bycatch sample) and a randomly-collected field sample. This enabled analysis of the proportion of E. bilobata specimens displaying the Sutural Gape and Salter's modes of moulting and their different configurations, and tests for association between moulting behaviour and body proportions. The results show a wide range of E. bilobata moulting configurations in all samples, suggesting that configurations represent definable instances in a largely continuous spectrum of variation. Analyses comparing body proportions of specimens showing the two modes of moulting were non-significant, suggesting there is no true association between moulting behaviour and body proportion, except for a single significant result for body length. All results were relatively consistent between the museum and field samples. However, removing accessioned specimens from the museum sample brought results even further in line with the field sample, supporting the need for consideration of museum collection bias in palaeontological analyses.     

Sensitivity of trapezius electromyography to differences between work tasks - influence of gap definition and normalisation methods.

Surface electromyography (EMG) has been used extensively to estimate muscular load in studies of work related musculoskeletal disorders, especially for the trapezius muscle. The occurrences of periods of EMG silence (gaps), the time below a predetermined threshold level (muscular rest) and various percentiles of the amplitude distribution (APDF) are commonly used summary measures. However, the effects of the criteria used to calculate these measures (e.g., gap duration, threshold level, normalisation method) on the sensitivity of these measures to accurately differentiate work loads is not well known.Bilateral trapezius EMG was recorded, for a full workday, for 58 subjects following both maximal (MVE) and submaximal (RVE) reference contractions. Gap frequency, muscular rest, and percentiles were derived for eight fundamental work tasks. The calculations were performed using different gap duration criteria, threshold levels and normalisation methods.A gap duration of less than 1/2 s, and threshold level approximately 0.3% MVE for gap frequency, and approximately 0.5% MVE for muscular rest, were the criteria that optimised sensitivity to task differences. Minimal sensitivity to tasks and a high sensitivity to individuals was obtained using gap frequency with a threshold level of approximately 1% MVE. Normalisation to RVE, rather than MVE, improved sensitivity to differences between tasks, and reduced undesirable variability. Muscular rest was more sensitive to task differences than APDF percentiles.     

Interactions in vitro and in vivo between anionic and cationic porcine trypsin and porcine plasma proteinase inhibitors

A method for purifying porcine anionic and cationic trypsin is presented. Reaction mixtures with increasing amounts of the two porcine trypsins and porcine serum were studied in vitro to evaluate the relative importance of alpha 1-macroglobulin and alpha 2-macroglobulin as well as alpha 1-proteinase inhibitor in the rapid binding of porcine anionic and cationic trypsin. Porcine cationic trypsin was preferentially bound to alpha 1-macroglobulin, while anionic trypsin exhibited equal binding to both alpha-macroglobulins. Both trypsins were also bound by the alpha 1-proteinase inhibitor but not until alpha 1-macroglobulin approached saturation. Trypsin-alpha-macroglobulin complexes were cleared from plasma with a half-life of 6 min. For trypsin-alpha 1-proteinase inhibitor-complexes the half-life was 120 min. These findings are in accordance with results for other mammalian species, including man.     

Identification of covalent binding sites of ethyl 2-cyanoacrylate,methyl methacrylate and 2-hydroxyethyl methacrylate in human hemoglobin using LC/MS/MS techniques

Acrylates are used in vast quantities, for instance in paints, adhesive glues, molding. They are potent contact allergens and known to cause respiratory hypersensitivity and asthma. Here we study ethyl 2-cyanoacrylate (ECA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). There are only limited possibilities to measure the exposure to acrylates, especially for biological monitoring. The aim of the present study was to investigate the chemical structures of adducts formed after reaction of hemoglobin (Hb) with ECA, MMA, and HEMA. This information may be used to identify adducted Hb peptides for biological monitoring of exposure to acrylates. Hb-conjugates with ECA, MMA, and HEMA were synthesized in vitro. The conjugates were digested by trypsin and pronase E. Adducted peptides were characterized and analyzed by liquid chromatography and nano electro spray/hybrid quadrupole time-of-flight mass spectrometry (MS) as well as tandem quadrupole MS. The search for the adducted peptides was facilitated by visualizing the MS data by different computer programs. The results showed that ECA binds covalently to cysteines at the 104 position in the α and the position 112 in the β-chains in Hb. MMA and HEMA bound to all the cysteines in both chains, Cys¹⁰⁴ in the α-chain and Cys⁹³ and 112 in the β-chain. The full-length spectra of in un-digested Hb confirmed this binding pattern. There was no reaction with N-acetyl-l-lysine at physiological pH. The adducted peptides were possible to measure using LC/MS/MS in selected reaction monitoring mode. These peptides may be used for biological monitoring of exposure to ECA, MMA and HEMA.     

Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis

Objective To review outcomes in randomised controlled trials comparing hydralazine against other antihypertensives for severe hypertension in pregnancy.Study design Meta-analysis of randomised controlled trials (published between 1966 and September 2002) of short acting antihypertensives for severe hypertension in pregnancy. Independent data abstraction by two reviewers. Data were entered into RevMan software for analysis (fixed effects model, relative risk and 95% confidence interval); in a secondary analysis, risk difference was also calculated.Results Of 21 trials (893 women), eight compared hydralazine with nifedipine and five with labetalol. Hydralazine was associated with a trend towards less persistent severe hypertension than labetalol (relative risk 0.29 (95% confidence interval 0.08 to 1.04); two trials), but more severe hypertension than nifedipine or isradipine (1.41 (0.95 to 2.09); four trials); there was significant heterogeneity in outcome between trials and differences in methodological quality. Hydralazine was associated with more maternal hypotension (3.29 (1.50 to 7.23); 13 trials); more caesarean sections (1.30 (1.08 to 1.59); 14 trials); more placental abruption (4.17 (1.19 to 14.28); five trials); more maternal oliguria (4.00 (1.22 to 12.50); three trials); more adverse effects on fetal heart rate (2.04 (1.32 to 3.16); 12 trials); and more low Apgar scores at one minute (2.70 (1.27 to 5.88); three trials). For all but Apgar scores, analysis by risk difference showed heterogeneity between trials. Hydralazine was associated with more maternal side effects (1.50 (1.16 to 1.94); 12 trials) and with less neonatal bradycardia than labetalol (risk difference -0.24 (-0.42 to -0.06); three trials).Conclusions The results are not robust enough to guide clinical practice, but they do not support use of hydralazine as first line for treatment of severe hypertension in pregnancy. Adequately powered clinical trials are needed, with a comparison of labetalol and nifedipine showing the most promise.     

Precision of measurements of physical workload during standardised manual handling. Part II: Inclinometry of head, upper back, neck and upper arms.

For measuring the physical exposure/workload in studies of work-related musculoskeletal disorders, direct measurements are valuable. However, the between-days and between-subjects variability, as well as the precision of the method per se, are not well known. In a laboratory, six women performed three standardised assembly tasks, all of them repeated on three different days. Triaxial inclinometers were applied to the head, upper back and upper arms. Between-days (within subjects) and between-subjects (within tasks) variance components were derived for the 10th, 50th and 90th percentiles of the angular and the angular velocity distributions, and for the proportion of time spent in predefined angular sectors. For percentiles of the angular distributions, the average between-days variability was 3.4 degrees , and the between-subjects variability 4.0 degrees . For proportion of time spent in angular sectors, the variability depended on the percentage of time spent in the sector; the relative variability was scattered and large, on average 103% between days and 56% between subjects. For the angular velocity percentiles, the average between-days variability was 7.9%, and the average between-subjects variability was 22%. The contribution of the measurement procedure per se to the between-days variability, i.e., the imprecision of the method, was small: less than 2 degrees for angles and 3% for angular velocity.     

Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma

 Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF-R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed against EGF-R was produced for therapeutic use. Eight patients with primary or recurrent, EGF-R-positive glioblastomas entered the study, which was designed to evaluate the clinical effect of the mAb. In order to achieve a high tumor cell saturation, the mAb was injected intratumorally twice weekly through an implantable catheter. The total administered dose varied between 4 mg and 120 mg. In 3 patients with solid tumors, a massive tumor necrosis was noted, with infiltration of macrophages, granulocytes and T cells. A further 3 patients developed clinical and radiological signs of an intense, local, inflammatory reaction. There may be a relation between the mAb dosage and the antitumor effect, insofar as higher doses seemed to cause a more pronounced, inflammatory reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable necrosis in glioblastoma. However, the planned schedule could not be completed, even after the dose level was re-adjusted, owing to inflammatory reactions, which were severe without prior tumor debulking. Received: 12 November 1996 / Accepted: 3 March 1997