The effects of serotonin on prolactin and growth hormone concentrations in normal and pituitary stalk-sectioned monkeys.

The effects of serotonin on PRL and GH secretion were studied in normal and pituitary stalk-sectioned female rhesus monkeys. Serotonin was administered iv at doses of 50, 500, 5000 microgram. Pretreatment concentrations of serum PRL were elevated in stalk-sectioned monkeys compared to normal monkeys [34 +/- 5 vs. 3 +/- 1 ng/ml (mean +/- SEM)], while serum GH concentrations were lower in the stalk-sectioned animals (< 0.5 vs. 1.3 +/- 0.2 ng/ml). In both normal and stalk-sectioned monkeys, the 5-microgram dose of serotonin failed to alter PRL concentrations. However, with the 500-microgram dose, PRL rose from 3 +/- 1 to 22 +/- 6 ng/ml in normal monkeys and from 27 +/- 6 to 57 +/- 10 ng/ml in stalk-sectioned monkeys. Likewise, with the 5000-microgram dose, PRL rose from 4 +/- 2 to 82 +/- 27 and from 30 +/- 6 to 75 +/- 26 ng/ml in the two respective groups. No dose of serotonin stimulated GH secretion in stalk-sectioned monkeys, although GH did increase from approximately 2 to 4-11 ng/ml in normal monkeys. Since the pituitary is devoid of direct hypothalamic influences in the pituitary stalk-sectioned animals, these results suggest that serotonin can modulate PRL secretion either directly at the pituitary level or via some yet to be determined peripheral mechanism. In contrast, this neurotransmitter appears to incorporate hypothalamic factors in its modulation of GH secretion.

Dopaminergic and serotonergic involvement in opiate-induced prolactin release in monkeys.

The present experiments were performed to determine the site of action (hypothalamic or hypophyseal) and the mechanism (dopaminergic or serotonergic) by which morphine increases PRL in monkeys (Macaca mulatta and Macaca nemestrina). To determine the site of action, 9 mg morphine were injected iv to four intact and four pituitary stalk-sectioned monkeys. PRL concentrations rose significantly (P less than 0.01) from less than 5 ng/ml to an average maximum value of 208 +/- 20 ng/ml at 15 min in intact animals, but remained unchanged in pituitary stalk-sectioned animals. There was a significant reduction (P less than 0.01) of this response in intact monkeys that received 5 mg L-dopa, iv, 5 min before the morphine stimulus. In these animals, PRL only rose to 100 +/- 46 ng/ml. In contrast, the PRL response in four monkeys pretreated with 5 or 20 mg methysergide, iv (a serotonin receptor blocker), 5 min before the opiate stimulus was not different from in controls. Likewise, the daily administration of 100 mg p-chlorophenylalanine, sc (a serotonin synthesis blocker), for 6 days failed to alter the PRL response to morphine. These data suggest that opiates increase PRL via a neural site of action and that the mechanism may involve dopaminergic but not serotonergic pathways.

Detection and partial characterization of a specific plasminogen activator inhibitor in human chondrocyte cultures.

Serum-free culture medium collected from primary monolayer cultures of human articular chondrocytes was found to inhibit human urokinase [EC 3.4.21.31] activity. Although chondrocyte culture medium contained a small amount of endothelial-type plasminogen activator inhibitor which could be demonstrated by reverse fibrin autography, most of the urokinase inhibitory activity of chondrocyte culture medium was shown to be due to a different molecule from endothelial-type inhibitor, since it did not react with a specific antibody to this type of inhibitor. The dominant urokinase inhibitor in chondrocyte culture medium was partially purified by concanavalin A-Sepharose affinity chromatography. The partially purified inhibitor inhibited high-Mr urokinase more effectively than low-Mr urokinase, but no obvious inhibition was detected against tissue-type plasminogen activator, plasmin, trypsin, and thrombin. The inhibitor had an apparent Mr of 43,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis, and it was unstable to sodium dodecyl sulfate, acid, and heat treatments. Inhibition of urokinase by the inhibitor was accompanied with the formation of a sodium dodecyl sulfate-stable high-Mr complex between them. Inhibition and complex formation required the active site of urokinase. The partially purified inhibitor was thought to be immunologically different from the known classes of plasminogen activator inhibitors, including endothelial-type inhibitor, macrophage/monocyte inhibitor, and protease nexin, since it did not react with specific antibodies to these inhibitors.

Language changes in schizophrenia: a limited replication.

Similar changes in the spoken language of schizophrenic patients were demonstrated in two separate studies. Schizophrenic patients used less depth of clausal embedding and fewer reduced relative clauses; they uttered more semantically deviant sentences and were more dysfluent than either manic patients or control subjects. They appeared to demonstrate a language impairment characterized especially by reduced syntactic complexity. Four linguistic variables in a discriminant analysis produced an overall diagnostic confidence for schizophrenia in "grouped" subjects of 87 percent, replicating at 83 percent for "ungrouped" subjects from a separate study. These results demonstrate the stability of language changes in schizophrenia, together with acceptable levels of diagnostic sensitivity and specificity. Currently, the possible diagnostic utility of language analysis is constrained by its time-consuming nature. The issue of whether the language changes represent a specific (linguistic) or general cognitive impairment is being addressed in a second phase of the current study.

The comprehension and production of complex syntax in schizophrenia.

A new and syntactically more complex version of the Token Test was developed to investigate the comprehension of complex syntax in schizophrenia. Results suggested that schizophrenic patients as a group demonstrated an impairment of comprehension proportionate to a reduction in the syntactic complexity of their spoken language, which had been demonstrated in two separate studies. While manic patients also recorded poorer results on the new Token Test than control subjects, there were no significant correlations between their comprehension and production measures as there were for the schizophrenic patients. The speculation is made that manic patients may perform poorly because of state factors such as distractibility, while schizophrenic patients may do so because of an underlying language impairment.

Feedback as a source of information and as a source of noise in absolute judgments of loudness.

Two experiments investigated the effects of feedback on absolute judgements of loudness. In Experiment 1, subjects received aceurate, unreliable, or no feedback. While feedback improved the information transmitted in judgments, it gave lower d' values than no feedback. These results were not compatible with a signal detection model with a noisy sensory stage and a decision stage with a fixed criterion, but suggested that criteria move in response to feedback and thus contribute judgmental noise to perceptual processes. Further confirmation for a variable criterion was obtained in Experiment 2, where reliability of feedback was held constant, but feedback was biased to favor some response alternatives more than others. Biased feedback shifted the positions of criteria, but also increased the inertia of some criteria in responding to feedback which caused changes in d'.

Supramalleolar derotation osteotomy for lateral tibial torsion and associated equinovarus deformity of the foot.

The development of lateral tibial torsion in the paralysed lower limb is well documented, but its pathogenesis is poorly understood. This paper attempts to provide an explanation for its development when it is associated with a varus or equinovarus deformity of the hindfoot. Correction of the lateral tibial torsion by supramalleolar derotation tibial osteotomy and reorientation of the ankle mortise appear to unlock the talus from the laterally rotated position, correcting a mobile hindfoot varus deformity and altering soft-tissue tensions about the ankle so that the correction achieved is maintained. In the presence of a fixed hindfoot deformity, supramalleolar derotation tibial osteotomy is useful as a first-stage procedure before corrective osteotomies of the foot. The operation described is technically simple and carries a low morbidity. Twenty supramalleolar derotation tibial osteotomies in 18 patients have been performed with satisfactory results and few complications.

Relationships between lake chemistry and calcium and trace metal concentrations of aquatic invertebrates eaten by breeding insectivorous waterfowl.

Ca, P, Al, and trace metal (Cu, Ni, Zn, Cd, and Pb) concentrations were measured in several aquatic invertebrate taxa used as food by breeding insectivorous waterfowl, sampled from three sites in eastern Canada with widely varying water chemistry. Ca concentrations were highest in molluscs (snails and clams), averaging 200-300 mg g(-1) (shells included). Aquatic insects of varying sizes, life stages and habits (caddisfly larvae, dragonfly larvae, adult backswimmers, waterstriders, and whirligig beetles) had much lower mean Ca concentrations, ranging from about 0.6 mg g(-1) (beetles) to 1.8 mg g(-1) (caddisflies). Invertebrate-Ca concentrations decreased with increasing body mass for several taxa, with smaller and larger individuals providing similar absolute amounts of Ca. Ca concentrations in most aquatic insects (but not molluscs) were reduced under acidic, low Ca, high Al, low dissolved organic carbon (DOC) and/or low total phosphorus (TP) conditions. In stepwise multiple regressions, pH was consistently the main factor explaining variability in invertebrate-Ca, after controlling for the negative relationship between invertebrate-Ca and body mass for some taxa. Molluscs were absent from lakes below pH 5.3. In general, concentrations of P and metals in invertebrate taxa were not significantly correlated with lake pH. Levels of Al, Cd, or Pb were not sufficiently high to be considered toxic to potential consumers of these organisms. For waterfowl and other birds breeding in acid-stressed habitats and relying on aquatic invertebrates as a source of food, a reduced availability of dietary Ca is more likely than an increased exposure to toxic metals to negatively affect reproductive success, especially when other adverse effects of acidification (lower diversity of prey) are considered.

Leeches as indicators of dietary mercury exposure in non-piscivorous waterfowl in central Ontario, Canada.

We collected and analysed 113 leeches (Hirudinea) from 17 small lakes in the acid-stressed Muskoka region of central Ontario, Canada to examine the relationship between lake chemistry and mercury (Hg) concentrations in leeches, and thus determine whether leeches and other benthic invertebrates posed a dietary risk of Hg exposure for non-piscivorous waterfowl. Hg concentrations in leeches were generally low and only a few-fold above the detection limit (0.78 ng g(-1) wet weight (ww)). Mean Hg concentration in the bloodsucker Macrobdella decora was 6.94 +/- 0.78 SE ng g(-1) ww (n=49) and was 5.98 +/- 0.46 ng g(-1) ww (n=64) in the scavenger Percymoorensis marmoratis. Leech Hg concentrations were correlated with calcium and dissolved organic carbon concentrations in the water, respectively. These data suggest that leeches are not suitable monitors of Hg (usually as methylmercury) biomagnification in central Ontario lakes, and do not pose a dietary risk to non-piscivorous waterfowl.

Towards a model of acidification effects on waterfowl in Eastern Canada.

Data from 212 lakes in central Ontario were used to examine the relationship between presence of breeding waterfowl and loons and the following lake characteristics: pH, presence of fish, lake area, dissolved organic carbon (DOC) and total phosphorus (TP) concentration. In univariate analyses, the two fish-eating species preferred large, high pH lakes with fish, while insectivorous species showed little consistent pattern of lake association. Logistic regression analyses confirmed that large lake size and presence of fish were important determinants of presence of piscivores, though the residual effect of pH differed between the two species. Broods of three of the four insectivorous species avoided lakes with fish, and independently showed a positive response to pH. By calculating the probability that fish will be present on a lake of given area and pH, it is possible to estimate the net effect of pH change on these waterfowl. Relationships such as those presented here can, with some assumptions, be linked to models of lake acidification to estimate response of waterfowl to predicted changes in acidic deposition.

Cell receptors to sulphated polysaccharides in the acute and chronically inflamed synovial joint.

Receptors to sulphated polysaccharides have recently been discovered on "free" joint fluid cells and synovial membrane cells in the normal joint. A search for these receptors on cells was made in rabbits with acute and chronic adjuvant inflammatory arthritis in an attempt to further elucidate their role in joint homeostasis. These experiments demonstrated a significant increase in cell numbers within the joint. Receptor activity was most marked on macrophages found free within the synovial fluid. It is postulated that exogenous cells may be important in the process of joint destruction and are outside the control of the normal joint regulatory mechanisms. The endogenous cell population, which exhibits receptor activity, may be responding to the process of joint destruction by proliferation as a secondary phenomenon.

Extraction and characterization of proteoglycan from human meniscus.

This study consists of (1) the extraction of proteoglycan from the human meniscus under dissociative conditions, (2) an investigation of the changes that occur in the abundance and structure of this proteoglycan with age and (3) a comparison of these findings with those for human articular-cartilage proteoglycan. Adult meniscus was found to possess proteoglycan molecules of similar size and glycosaminoglycan content to those present in cartilage, although tissue concentrations were considerably lower. In addition, age-related changes, with respect to the occurrence of keratan sulphate and the sulphation of chondroitin sulphate chains, were common to both tissues. The presence of aggregated proteoglycan was demonstrated, although specific interaction with hyaluronic acid was not conclusively shown biochemically. Differences were, however, noted in the structure of the proteoglycan between the two tissues: dermatan sulphate was found in the meniscus proteoglycan preparation and the core proteins exhibited some dissimilarities. A proteoglycan structure of this type would be compatible with its participation in meniscus elasticity, especially as the material is localized in a specific area.

The Premorbid Adjustment Scale (PAS): its use in an Australian study.

The Premorbid Adjustment Scale (PAS) is a new premorbid scale for use in schizophrenia, developed by the National Institute of Mental Health. Its use in a recent Australian study is described. While total scores clearly discriminated schizophrenic from manic patients, and good test-retest reliability was demonstrated for the schizophrenic patients, the scores did not predict duration of hospitalisation for the schizophrenic group, as reported in the North American study. It is concluded that more research on the PAS is necessary before it can be accepted as a useful instrument in schizophrenia research and clinical practice.

Modality-specific differences in the processing of spatially, temporally, and spatiotemporally distributed information.

The extent to which auditory, tactile, and visual perceptual representations are similar, particularly when dealing with speech and speech-like stimuli, was investigated. It was found that comparisons between auditory and tactile patterns were easier to perform than were similar comparisons between auditory and visual stimuli. This was true across a variety of styles of tactile and visual display, and was not due to limitations in the discriminability of the visual displays. The findings suggest that auditory and tactile representations of stimuli are more alike than are auditory and visual ones. It was also found that touch and vision differ in terms of the style of information distribution which they process most efficiently. Touch dealt with patterns best when the pattern was characterised by changes across time, whereas vision did best when spatially or spatiotemporally distributed patterns were presented. As the sense of hearing also seems to specialise in the processing of temporally ordered patterns, these results suggest one way in which the senses of hearing and touch differ from vision.

Human articular cartilage contains an inhibitor of plasminogen activator.

The presence of plasminogen activator (PA) inhibitor in human articular cartilage extracts was shown using a microtiter plate assay using immunofixed urokinase. Cartilage urokinase inhibitor had a molecular weight of 66,000 on gel chromatography. Cartilage extracts also contained alpha 1-proteinase inhibitor; however, the urokinase inhibitor was distinguishable from such serum inhibitors immunologically. In sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by fibrin overlay, inhibition of urokinase was observed accompanying higher molecular weight complex formation. The cartilage urokinase inhibitor was unstable with acid, heat and SDS treatment, and required the active site of urokinase for inhibition.

The presence of a cartilage-like proteoglycan in the adult human meniscus.

Proteoglycans were extracted from the adult human meniscus under dissociative conditions and purified by CsCl-density-gradient centrifugation. The preparations of highest density contained proteoglycan that possessed the ability to interact with hyaluronic acid, was of large subunit size and was composed of chondroitin sulphate, keratan sulphate and sialic acid-containing oligosaccharides. This 'cartilage-like' proteoglycan also exhibited subunit and aggregate structures analogous to those of hyaline-cartilage proteoglycans when examined by electron microscopy. However, the composition of this proteoglycan was more comparable with proteoglycans from immature cartilage than from age-matched cartilage. The preparations from lower density, which were enriched in dermatan sulphate, contained smaller proteoglycan that was not able to interact with hyaluronic acid. This non-aggregating proteoglycan may be structurally distinct from the 'cartilage-like' proteoglycan, which does not contain dermatan sulphate.

Supracondylar fractures of the femur in children.

Nonphyseal supracondylar fractures of the femur are considered to be uncommon in children and have received little attention in the literature. A retrospective review of femoral fractures in children at the authors' institution was undertaken to ascertain the incidence of supracondylar femoral fractures, the influence of associated musculoskeletal conditions, and pitfalls of management. In this study of 102 femoral fractures, there was an incidence of 12% of supracondylar fractures. Four of 12 patients had a significant predisposing musculoskeletal condition contributing to the genesis of the fracture. Five fractures were undisplaced and easily managed. Seven displaced fractures required intervention to achieve an adequate reduction. The literature is reviewed and a classification system for these fractures is presented. Treatment options are discussed and recommendations made based on this experience.