Adjustable sutures in squint surgery.
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Biomedical subjects
Publications and source records attributed to R J Morris.
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Tissue and urokinase-type plasminogen activators are serine proteases with highly restricted specificity, their best characterised role being to release the broad specificity protease plasmin from inactive plasminogen. It has frequently been suggested that these, and similar proteases, are involved in axonal growth and tissue remodelling associated with neural development. To help define what this role might be, we have studied the expression of the plasminogen activators in developing rat nervous tissue. Urokinase-type plasminogen activator mRNA is strongly expressed by many classes of neurons in peripheral and central nervous system. We have analysed its appearance in spinal cord and sensory ganglia, and found the mRNA is detectable by in situ hybridisation very early in neuronal development (by embryonic day 12.5), at a stage compatible with it playing a role in axonal or dendritic growth. Tissue plasminogen activator mRNA, on the other hand, is expressed only by cells of the floor plate in the developing nervous system, from embryonic day 10.5 and thereafter. Immunohistochemical and enzymatic analysis showed that active tissue plasminogen activator is produced by, and retained within, the floor plate. A mechanism is suggested by which high levels of tissue plasminogen activator produced by the stationary cells of the floor plate could influence the direction of growth of commissural axons as they pass through this midline structure.
A study to assess the effect of the long-term use of triamcinolone acetonide (TA) on adrenal function was conducted with 143 male and female patients with asthma who were randomly assigned to receive 800, 1200, or 1,600 micrograms of TA daily for six months. Adrenal function was assessed prior to treatment and after two weeks and one, three, and six months of TA use. The effect of TA was evaluated by measuring plasma cortisol levels just prior to and 30 min after a bolus IV injection of 0.25 mg cosyntropin. Adrenal suppression was assumed if the plasma concentration of cortisol did not increase by at least 7 micrograms/dl from the prestimulation value, and remained below 18 micrograms/dl 30 min after the cosyntropin injection. Urine collected for 24 h prior to each cosyntropin stimulation was assayed for free cortisol and related metabolites to confirm suppression. Although all treatment regimens caused some reduction in the 24-h excretion of corticosteroid products, none of the mean values was below the normal ranges. The mean data indicate that TA had no significant effect on adrenal function at any dose or at any time for the patients overall. Individually, three patients exhibited some reduction in adrenal function.
At four medical centers, 98 patients with stable asthma, histories of nighttime awakening at least three times weekly and nighttime declines of pulmonary function of at least 15%, who were not taking oral adrenergic agonists, were randomly treated with either oral repeat-action albuterol sulfate (Proventil Repetabs), 4 mg in the morning and 4-16 mg at bedtime, or a placebo for 2 weeks. All patients were required to have nocturnal symptoms of asthma, with prior use of bronchodilators other than oral adrenergic agonists to be eligible for the study. The patients maintained a diary of asthma symptom scores and recorded peak flow rates at home at bedtime and in the morning. They had spirometry (FEV1, FVC, and PEFR) after a 1-week baseline stabilization period, and after 1 and 2 weeks of double-blind oral therapy as noted above. Efficacy was evaluated by changes in the bedtime and morning peak flow rates, changes in the number of nighttime awakenings, results of office spirometry testing, and by physician and patient global evaluations of response to therapy. Of the 98 patients in the study, 47 received oral albuterol, and 51 received placebo. The patients on albuterol had a statistically significant reduction in the number of nighttime awakenings (p less than or equal to 0.01), as compared with the patients on placebo; this included both the average number of awakenings per week (p = 0.04), and the mean number of nights with awakenings per week (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
A chemically defined medium containing 1.2 mM Ca2+ has been developed for the culture of primary epidermal keratinocytes from untreated adult mice such that proliferation is accompanied by the formation of desmosomes and stratification. Cultured cutaneous explants of 1 mm2 from the backs of untreated, control, and carcinogen-exposed mice all demonstrated epithelial outgrowth within 1 wk, and by 5 wk approached confluence with characteristics of terminal differentiation such as desmosomes and stratification. Addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the medium in concentrations of 0.001, 0.01, and 0.1 micrograms/ml resulted in a delay of approximately 1 wk in the outgrowth of the explants compared with the acetone controls and in a 30% decrease in the diameter of the epithelial outgrowth at 3 wk. The inhibition in outgrowth was overcome at higher concentrations (0.5, 1.0, and 10 micrograms/ml TPA). No obvious differences in morphology or in the rate of epidermal outgrowth within a 5-wk interval among explants from normal untreated epidermis, epidermis from mice treated with acetone, or epidermis from mice treated with an initiating application of 7,12-dimethylbenz[a]anthracene were observed. The defined composition of this medium and its ability to support reproducibly and conveniently both proliferation and differentiation of normal as well as treated primary adult murine epidermal cells suggest that it should be useful for a number of studies not previously possible that are relevant to the biology of the skin, to toxicology, and to carcinogenesis in the murine model system.
The use of structural equation modeling has gained increased interest in recent years in the social and behavioral sciences. This article reviews the basic tenets of structural modeling in relation to issues in research and practice involving clinical assessment and compares this approach with more traditional psychometric approaches to the validation of assessment instruments with children. Arguments for and against the inclusion of nonexperimental variables in causal studies aimed at establishing construct validity are also discussed. An illustrative example of the application of structural equation modeling in clinical assessment research is provided, and a comparison is made between this approach and traditional psychometric procedures. Implications and suggestions for the use of structural modeling are discussed for both the practitioner and the clinical researcher.
When children or adolescents are clients in receipt of psychological treatment, there are specific issues that require attention. With regard to assessment and diagnosis, researchers and clinicians alike must pay attention to variations across sources of assessment data, the comorbidity of diagnoses, and the potential utility of a "family" (as opposed to child) diagnosis. Considerations of "Who is the client?" and the role of the therapeutic relationship in child therapy are discussed. Specific methodological recommendations regarding randomized clinical trials, control groups, the selection of dependent variables, the manualization of treatments, and the use of tests of clinical and statistical significance are presented. Specific topics for research are recommended.
All patients presenting with double vision as a principal symptom who presented to the Casualty Department of Moorfields Eye Hospital over a nine month period were prospectively investigated. Two hundred and seventy five patients were identified accounting for 1.4% of all casualties. Monocular diplopia was commoner than expected accounting for 69 cases (25.1%) and was almost always a genuine symptom attributable to uniocular pathology, most commonly lenticular or corneal pathology. Two hundred and six patients (74.9%) had binocular diplopia and in most cases an aetiology was established. Cranial nerve palsies were the commonest cause of binocular diplopia accounting for 81 cases. Other causes were classified as convergence or accommodation problems, decompensating phorias, traumatic, muscular, orbital lesions, supranuclear lesions, and other miscellaneous conditions. In eight cases of monocular and 23 cases of binocular diplopia no cause for the symptoms could be identified.
Thy-1 is a developmentally regulated surface glycoprotein expressed on a number of tissues, including nerve where it is a major surface component of mature neurons. During neural development in the rat and mouse, expression of Thy-1 protein does not necessarily follow appearance of its mRNA, but additionally requires completion of the initial phase of axonal growth. Where there is a substantial lag phase between initial elongation and final axonal outgrowth into a terminal field (e.g. pontine projection to the cerebellum), Thy-1 protein appears at the cell body and dendrites of the neurons, but is excluded from their axons until the terminal phase of axonal growth is completed. In the more complex case of the vestibular ganglion neurons, whose axons project primarily to the vestibular nuclei in the brainstem before birth, and then 1-2 weeks later into the cerebellum, Thy-1 enters the proximal axonal regions where growth is completed, but not the distal growing ends. Thus complex controls govern the initial expression and distribution of Thy-1 so as to exclude it from growing regions of axons.
Eleven patients entered a pilot study designed to evaluate the proportion of eligible responders following a single inhalation of albuterol aerosol, the degree of response, and the sensitivity to distinguish between one and two inhalations based on FEV1 response. Each patient received a single inhalation at 0 and 60 minutes. FEV1 was measured 30 and 60 minutes after each inhalation. Most patients (82%) responded to a single inhalation and the majority (73%) were capable of further response after two inhalations. This study design was able to distinguish FEV1 responses to one and two inhalations of albuterol and provide upward and downward sensitivity sufficient to detect major differences in products.
T cells can be activated, not only by the conventional (antigen-receptor/CD3 complex) route, but also by cross-linking any one of their lipid-anchored surface glycoproteins. We have compared early transmembrane signalling events mediated through CD3 with those mediated through Thy-1, a lipid-linked surface glycoprotein, on the human lymphoid cell line Jurkat and transfectants expressing higher levels of Thy-1. Cross-linking of Thy-1 causes immediate phosphatidylinositol (PI) turnover and an influx of extracellular Ca2+, while releasing very little Ca2+ from intracellular stores. CD3 activation, on the other hand, causes PI turnover which releases intracellular Ca2+, and only secondarily induces an influx of extracellular ions. The Thy-1 response is detectable at very low levels of surface Thy-1, and is not mimicked by enzymatic removal of lipid-linked proteins from the cell surface. The Thy-1-induced Ca2+ influx is more sensitive to L channel blockers than the CD3-mediated flux. These results indicate that the initial stages of Thy-1-mediated activation involve the rapid and extensive mobilization of the intracellular second messengers, PI and Ca2+, by mechanisms separate to those activated by the antigen-receptor/CD3 complex.
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The objective of this randomized, single-blind, parallel group study was to determine whether a more constant rate of albuterol delivery from tablets provides less variability in bronchodilation. Thirty-eight adult patients were enrolled with FEV1 between 40% to 80% of predicted normal and greater than or equal to 15% reversibility. Eighteen patients received Volmax, 8 mg bid, and 20 patients received Proventil Repetabs, 8 mg (as two 4-mg tablets) bid. The magnitude and duration of bronchodilation were determined after the first dose and at steady state on treatment day 7 by measuring serial values of pulmonary function for 12 hours on each day. Interpatient variability in bronchodilation was calculated for each study day did not differ significantly between treatments, the interpatient variability in bronchodilation with Volmax was, on average, one-half of that experienced with Proventil Repetabs. Adverse events, mainly headache and tremor, were comparable between Volmax and Proventil Repetabs. This study demonstrates that Volmax achieves less variable bronchodilation through a more constant rate of drug delivery from the onset of therapy.
We studied two patients who had infantile malignant osteopetrosis, severe visual loss, and diminished electroretinogram amplitudes with visible macular chorioretinal degenerative changes. The findings support the hypothesis that a subgroup of patients with infantile malignant osteopetrosis exists in whom the visual loss is caused by a primary retinal degeneration that may be associated with generalized central nervous system neuronal degeneration.
The distribution of benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene (DMBA):DNA adducts was examined in five different subpopulations of SENCAR mouse epidermal cells separated based on buoyant density in continuous gradients of 61.5% Percoll. Three fractions consisted of primarily basal cells (Fractions 3 to 5), while two less dense fractions (Fractions 1 and 2) consisted of primarily differentiating keratinocytes. The levels of B(a)P and DMBA:DNA adducts were examined at 1 h, 6 h, 24 h, 72 h (except DMBA), and 28 days after a single topical application of an initiating dose. Among the basal cell subpopulations, the level of covalent B(a)P:DNA adducts in Fraction 5 cells was significantly higher (P less than 0.05) than Fractions 3 and 4 at every time point examined. On the other hand, B(a)P:DNA adduct levels in Fraction 5 were only significantly higher than Fraction 2 at 6 h and 72 h and not significantly different from Fraction 1 at any time point. With DMBA, no significant differences were initially observed in the levels of covalent DNA adducts among the various Percoll fractions at 1 h and 6 h after treatment. However, at 24 h and at 28 days. Fraction 5 cells had significantly higher (P less than 0.05) levels of covalent DMBA:DNA adducts than Fractions 1 to 4. To explore whether the observed differences in DNA adduct levels were due to differences in metabolic activation, we examined the levels of covalent adducts among epidermal subpopulations after topical application of (+/-)-anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (anti-BPDE). Interestingly, 3 h after treatment with anti-BPDE, significantly higher (P less than 0.05) levels of binding were found in Fraction 5 compared with Fractions 1 to 4. High-pressure liquid chromatographic analyses of B(a)P and DMBA:DNA adducts 6 h and 24 h after treatment did not show any significant differences in adduct profiles among the various subpopulations. These results demonstrate the presence and persistence of hydrocarbon:DNA adducts in all epidermal subpopulations isolated on continuous Percoll gradients for at least 28 days after treatment. Furthermore, of the three basal cell subpopulations, the most dense cells (Fraction 5) developed the highest DNA adduct levels within 24 h and retained these higher levels over 28 days. Finally, differences in DNA adduct levels among epidermal subpopulations do not appear to result from different metabolic capabilities of the cells. The potential significance of these results is discussed in terms of the process of skin tumor initiation.
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A 512-element diode-array spectroscopic detection system capable of acquiring multiple spectra at a rate of 5 ms per spectrum with an effective scan rate of 102.9 kHz has been constructed. Spectra with fewer diode elements can also be acquired at scan rates up to 128 kHz. The detector utilizes a Hamamatsu silicon photodiode-array sensor that is interfaced to Hamamatsu driver/amplifier and clock generator boards and a DRA laboratories 12-bit 160-kHz analog-to-digital converter. These are standard, commercially available devices which cost approximately $3500. The system is interfaced to and controlled by an IBM XT microcomputer. Detailed descriptions of the home-built detector housing and control/interface circuitry are presented and its application to the study of the reaction of horseradish peroxidase with hydrogen peroxide is demonstrated.