The influence of speed and size on avian terrestrial locomotor biomechanics: Predicting locomotion in extinct theropod dinosaurs.

How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete 'walking' and 'running' gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79-93% of the observed variation in kinematics and 69-83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation.

Using step width to compare locomotor biomechanics between extinct, non-avian theropod dinosaurs and modern obligate bipeds.

How extinct, non-avian theropod dinosaurs locomoted is a subject of considerable interest, as is the manner in which it evolved on the line leading to birds. Fossil footprints provide the most direct evidence for answering these questions. In this study, step width-the mediolateral (transverse) distance between successive footfalls-was investigated with respect to speed (stride length) in non-avian theropod trackways of Late Triassic age. Comparable kinematic data were also collected for humans and 11 species of ground-dwelling birds. Permutation tests of the slope on a plot of step width against stride length showed that step width decreased continuously with increasing speed in the extinct theropods (p < 0.001), as well as the five tallest bird species studied (p < 0.01). Humans, by contrast, showed an abrupt decrease in step width at the walk-run transition. In the modern bipeds, these patterns reflect the use of either a discontinuous locomotor repertoire, characterized by distinct gaits (humans), or a continuous locomotor repertoire, where walking smoothly transitions into running (birds). The non-avian theropods are consequently inferred to have had a continuous locomotor repertoire, possibly including grounded running. Thus, features that characterize avian terrestrial locomotion had begun to evolve early in theropod history.

Analysis of insulin in human breast milk in mothers with type 1 and type 2 diabetes mellitus.

Despite the important role that insulin plays in the human body, very little is known about its presence in human milk. Levels rapidly decrease during the first few days of lactation and then, unlike other serum proteins of similar size, achieve comparable levels to those in serum. Despite this, current guides for medical treatment suggest that insulin does not pass into milk, raising the question of where the insulin in milk originates. Five mothers without diabetes, 4 mothers with type 1, and 5 mothers with type 2 diabetes collected milk samples over a 24-hour period. Samples were analysed for total and endogenous insulin content and for c-peptide content. All of the insulin present in the milk of type 1 mothers was artificial, and c-peptide levels were 100x lower than in serum. This demonstrates that insulin is transported into human milk at comparable concentration to serum, suggesting an active transport mechanism. The role of insulin in milk is yet to be determined; however, there are a number of potential implications for the infant of the presence of artificial insulins in milk.

Episiotomy counts: trends and prevalence in Canada, 1981/1982 to 1993/1994.

BACKGROUND: The purpose of this study was to produce a minimum estimate of the prevalence of episiotomy use in Canada, and to investigate the trend in its use between 1981/1982 and 1993/1994. METHOD: A retrospective population case series study was conducted using hospital discharge abstracts. Outcome measures were the count of episiotomies performed during a 12-month period and the episiotomy rate per 100 vaginal births. RESULTS: For more than a decade, official statistics have significantly underreported episiotomy use by as much as 50 percent. In 1993/1994 at least 37.7 percent of women giving birth vaginally in Canada are known to have received an episiotomy. Between 1981/1982 and 1993/1994 its prevalence declined 29.1 percent, with the greatest decline occurring during the 1990s. This decline did not result from changes in parity in the population. The decrease in episiotomy use during this 13-year period is more than twice that found in the United States (a decline of only 13.6%). CONCLUSIONS: The reporting of official statistics on obstetric procedures in Canada should be modified to include all known cases of episiotomy. The observed downward trend in the rate of this procedure is encouraging, and is in the direction of evidence-based recommendations advocating its restrictive use.

Sample size estimation for comparing two or more treatment groups in clinical trials.

Methods for estimating required sample size for comparing two population means have been published. Most involve the use of complicated formulae and tables. These methods are limited to comparing two groups. Although techniques exist to determine sample sizes for comparing more than two groups, they are intrinsically far more complicated. A simple linear nomogram is proposed as a solution to these problems, and its use is illustrated with examples of parallel group, ordered parallel group and factorial designs.

Mitogenic responses of peripheral blood mononuclear cells of vervet monkeys (Cercopithecus aethiops): Apparent role of adherent cells.

Peripheral blood mononuclear cells (PBM) from normal vervet monkeys (Cercopithecus aethiops) were examined for blastogenic responses to concanavalin A (ConA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). The mitogen stimulated PBM in a dose-dependent manner. Response to ConA was apparently higher than for the other two mitogens. Cell density and mitogen concentration were critical parameters for optimal lymphocyte proliferation, an observation in line with that reported for other mammalian species. Depletion of an adherent cell population probably of monocyte/macrophage lineage from vervet PBM gave higher proliferative responses to both ConA and PHA, but the response without adherent cells to ConA was greater than the response without adherent cells to PHA. This latter finding is in contrast to what has been reported in many other species.

Sample size and power for comparing two or more treatment groups in clinical trials.

Methods for determining sample size and power when comparing two groups in clinical trials are widely available. Studies comparing three or more treatments are not uncommon but are more difficult to analyse. A linear nomogram was devised to help calculate the sample size required when comparing up to five parallel groups. It may also be used retrospectively to determine the power of a study of given sample size. In two worked examples the nomogram was efficient. Although the nomogram offers only 5% and 1% significance levels and can be used only for up to five treatment groups, this is sufficient for most researchers.

The systemic availability of meptazinol in man after oral and rectal doses.

We have studied the pharmacokinetics of the centrally-acting analgesic meptazinol after oral and rectal administration to 15 healthy men. Each subject took a standard 200 mg tablet orally and Witepsol H12 suppositories containing 75, 100, and 150 mg of the drug in a cross-over design. Meptazinol plasma concentrations were measured by HPLC using fluorescence detection and the pharmacokinetics determined. The tmax values for the 100 mg and 150 mg suppositories (median = 0.5 h) were statistically significantly shorter than for the tablet (median = 1.13 h), suggesting that meptazinol was more rapidly absorbed via the rectal route. Despite substantial intersubject variation in Cmax the plasma concentrations after rectal dosage were higher than after oral administration. There was a statistically significant (p less than 0.001) improvement in systemic availability for each of the suppository doses (mean approximately 15.5% compared with the oral tablet (mean approximately 4.5%).

The disposition of meptazinol after single and multiple intravenous administration to pregnant and non-pregnant women.

We have studied the disposition of the centrally-acting analgesic meptazinol in a group of age-matched non-pregnant and pregnant (36-38 weeks gestation) women. Ten non-pregnant and nine multiparous pregnant volunteers each received a single i.v. dose of meptazinol hydrochloride (equivalent to 25 mg base). A further group of 9 non-pregnant (including four of the original participants) and 10 multiparous pregnant subjects were given repeated i.v. doses of meptazinol hydrochloride (each equivalent to 10 mg base) at 30-min intervals for 2.5 h. Meptazinol plasma concentrations were determined by HPLC using fluorescence detection and the pharmacokinetic variables investigated. After single dosing there were no statistical differences in half-life, clearance, or apparent volume of distribution between the two groups, suggesting that the disposition of meptazinol was not altered by pregnancy. This was confirmed in the repeated dose study, in which no significant differences occurred in either the plasma concentrations achieved or in areas under the curves between the non-pregnant and pregnant subjects. Furthermore, the steady-state concentrations were comparable with those predicted from the single dose results. This indicates that there should be no requirement for dosage alteration of meptazinol during pregnancy.

Pharmacokinetics of meptazinol after parenteral administration in the elderly.

We have determined the pharmacokinetics of meptazinol after its intravenous and intramuscular administration in a crossover study in 7 elderly hospital in-patients (greater than 70 years), and have compared with the results from 14 healthy, young volunteers (ages 20-40 years). The systemic availability after i.m. administration was comparable to that after i.v. administration, a result consistent with the physicochemical properties of the drug. There was a slight, but statistically significant (p less than 0.01) prolongation in t1/2Z in the elderly (mean 2.93 h) compared with the young (mean 2.06 h). This was associated with a 25% lower clearance in the elderly rather than with any alteration in volume of distribution. However, these changes would not appear to be substantial enough to require a revised dosage recommendation for meptazinol for this age group.

Morphology of bronchogenic carcinoma in workers formerly exposed to crocidolite at Wittenoom Gorge in Western Australia.

Cytology and histology material from 46 bronchogenic carcinomas occurring in ex-workers from the Wittenoom crocidolite mine and mill in Western Australia and a matched random sample of 234 other bronchogenic carcinomas occurring in Western Australia over the same period were reviewed by a single histopathologist without knowledge of asbestos exposure status. Squamous-cell carcinomas formed 45.7% of the cancers in the asbestos-exposed group but only 32.5% of the cancers in the comparison group. This difference could not be explained by differences in smoking history between the two groups of lung cancer patients or in the type of histopathological material available for review. The excess of squamous-cell cancers was observed in subjects both with and without parenchymal asbestosis.

Comparison of the effects of therapeutic doses of meptazinol and a dextropropoxyphene/paracetamol mixture alone and in combination with ethanol on ventilatory function and saccadic eye movements.

The respiratory and psychomotor effects of a single oral dose of meptazinol (200 mg) and dextropropoxyphene (65 mg)/paracetamol (650 mg) mixture, was compared alone and in combination with ethanol (0.8 g kg-1). Peak saccade velocity following meptazinol or the dextropropoxyphene/paracetamol mixture was not significantly different from placebo. When each of the treatments was followed by ethanol administration, a significant decrease in saccade velocity (P less than 0.01) was seen. Given alone, neither of the analgesic drugs produced a significant change in the slope of the ventilatory response to hypercapnia. Ethanol did not affect the ventilatory response to hypercapnia when given alone or in combination with meptazinol, but when given with the dextropropoxyphene/paracetamol mixture, a significant reduction in the slope of the ventilatory response to hypercapnia occurred at 1.5 h (P less than 0.05) and 2 h (P less than 0.01) after administration of the analgesic drug. No pharmacokinetic interaction was demonstrated between ethanol and meptazinol or the dextropropoxyphene/paracetamol mixture in the doses used. In contrast to meptazinol, the dextropropoxyphene/paracetamol mixture interacts with ethanol on the ventilatory function.

Pharmacokinetics of meptazinol after single and multiple oral administration to elderly patients.

Oral administration of meptazinol (200 mg Meptid) to male and female geriatric patients (greater than 70 years) resulted in rapid absorption, with peak drug concentrations at 0.5 to 3 h after dosage. Subsequent elimination also proceeded rapidly with a half-life of 3.39 h (+/- 0.26 SEM) after a single dose and 4.97 h (+/- 0.80 SEM) after 13 consecutive 6-h doses. These values were not statistically different. There was no accumulation of meptazinol above that expected from the single-dose kinetics. Plasma protein binding of meptazinol was 33.8% (+/- 0.74 SEM). No sex difference was apparent in any of the pharmacokinetic parameters determined. Comparison of these results with those obtained in an earlier study in young volunteers showed that although the half-life of meptazinol was somewhat longer than the value of 2 h seen in the young, peak plasma concentrations after single and multiple dosing were similar for both age groups, implying that clearance remained largely unaltered. It was concluded that there was no pharmacokinetic basis for recommending a reduction in dosage when treating elderly patients with oral meptazinol.

Pharmacokinetics of the new analgesic, meptazinol, after oral and intravenous administration to volunteers.

The pharmacokinetics of meptazinol (Meptid) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vd beta) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean = 8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.

The differential diagnosis between biliary and alcoholic pancreatitis.

The presenting clinical details of 53 patients admitted with proven primary acute pancreatitis due to gall stones were compared with those of 31 patients in whom the disease was due to other causes. Ten statistically significant differences existed between the two groups (p less than 0.05). A computer data base for each group of patients was prepared by listing the relative frequency of symptoms and signs. A computer program was written to predict the likelihood of gall stones in patients suffering from acute pancreatitis and prediction was correct in 92% of patients. A predictive index devised from the presence of three of the significantly differing clinical features correctly identified gall stones in 82%. Subsequent computer analysis of the presenting clinical symptoms and signs on admission every patient with acute pancreatitis has confirmed the accuracy of this technique and has resulted in alteration in the management whereby cholecystectomy for biliary pancreatitis is performed at an early stage of the illness.

Prediction of gall-stone pancreatitis by computer.

The clinical features at presentation of 53 patients admitted with primary acute pancreatitis due to gall stones were compared with those of 31 patients in whom the disease was due to other causes. Between these two groups 10 significant differences existed. By listing the frequency of symptoms and signs for each group a computer data base was prepared and incorporated into a program used in the differential diagnosis of acute abdominal pain. A program written to predict the presence of gall stones in patients with acute pancreatitis was accurate in 92% of the patients studied. A predictive index devised from the presence of three of the significantly differing clinical features correctly identified 82% of patients with gall-stone pancreatitis. Predicting the presence of gall stones on admission by analysing the presenting symptoms and signs with a computer had an accuracy comparable to that of ultrasonography or radiology and may be of value in the management of patients with acute pancreatitis.

Adult pre-sacral teratoma.

The clinical details and management of an adult female patient with a pre-sacral teratoma causing obstructed labour are described.

Computer-aided prediction of gangrenous and perforating appendicitis.

The clinical details of 100 patients with proved acute appendicitis were compared with those of 100 patients with perforating or gangrenous appendicitis. Twenty features were found to be significantly different between the two groups. This information was incorporated into a computer data base and used in the differential diagnosis of abdominal pain. A program written to predict the probability that gangrene or perforation was present in patients with appendicitis gave a diagnostic accuracy over 91%. A clinical scoring index, which accurately predicted the state of the appendix in 88% of patients, was constructed from the significant differences between the two groups. When clinical scoring or computer analysis predicts a high probability of perforation or gangrene in patients with appendicitis, surgery should be performed without delay.