Showing papers by "McMaster University published in 1988"

Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee.

Abstract: Within the context of a double blind randomized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs, we validated WOMAC, a new multidimensional, self-administered health status instrument for patients with osteoarthritis of the hip or knee. The pain, stiffness and physical function subscales fulfil conventional criteria for face, content and construct validity, reliability, responsiveness and relative efficiency. WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials.

Neural adaptation to resistance training.

Abstract: Strength performance depends not only on the quantity and quality of the involved muscles, but also upon the ability of the nervous system to appropriately activate the muscles. Strength training may cause adaptive changes within the nervous system that allow a trainee to more fully activate prime movers in specific movements and to better coordinate the activation of all relevant muscles, thereby effecting a greater net force in the intended direction of movement. The evidence indicating neural adaptation is reviewed. Electromyographic studies have provided the most direct evidence. They have shown that increases in peak force and rate of force development are associated with increased activation of prime mover muscles. Possible reflex adaptations related to high stretch loads in jumping and rapid reciprocal movements have also been revealed. Other studies, including those that demonstrate the "cross-training" effect and specificity of training, provide further evidence of neural adaptation. The possible mechanisms of neural adaptation are discussed in relation to motor unit recruitment and firing patterns. The relative roles of neural and muscular adaptation in short- and long-term strength training are evaluated.

Alternative Transformations to Handle Extreme Values of the Dependent Variable

Abstract: Transformations that could be used to reduce the influence of extreme observations of dependent variables, which can assume either sign, on regression coefficient estimates are studied in this article. Two that seem reasonable on a priori grounds—the extended Box—Cox (BC) and the inverse hyperbolic sine (IHS)—are evaluated in detail. One feature is that the log-likelihood function for IHS is defined for zero values of the dependent variable, which is not true of BC. The double-length regression technique (Davidson and MacKinnon 1984) is used to perform hypothesis tests of one transformation against the other using Canadian data on household net worth. These tests support the use of IHS instead of BC for this data set. Empirical investigators in economics often work with a logged dependent variable (taking the natural logarithm of a data series is, of course, a special case of BC) to reduce the weight their particular estimation procedure might otherwise attach to extreme values of the dependent v...

Ontario Child Health Study: Reliability and Validity of the General Functioning Subscale of the McMaster Family Assessment Device

Abstract: The reliability and validity of the 12-item General Functioning (GF) subscale of the McMaster Family Assessment Device (FAD) is reported here. Psychometric properties of the FAD have been previously determined, but no independent assessment has been made of the GF subscale, which was used to measure family functioning in the Ontario Child Health Study (OCHS). Reliability was measured by Chronbach's alpha and split-half correlation. Validity was assessed by hypothesizing the relationships expected between the GF scores and other family variables included in the OCHS data set. The results indicate good reliability, and all hypotheses of validity were supported. The brevity and ease of administering the GF subscale recommend it for further use in survey research in which a global assessment of family functioning is required.

A herpes simplex virus mutant in which glycoprotein D sequences are replaced by beta-galactosidase sequences binds to but is unable to penetrate into cells.

Abstract: Herpes simplex virus (HSV) glycoprotein gD is a major component of the virion envelope and is thought to play an important role in the initial stages of viral infection and stimulates the production of high titers of neutralizing antibodies. We assumed that gD plays an essential role in virus replication, and so to complement viruses with mutations in the gD gene we constructed a cell line, denoted VD60, which is capable of expressing high levels of gD after infection with HSV. A recombinant virus, designated F-gD beta, in which sequences encoding gD and a nonessential glycoprotein, gI, were replaced by Escherichia coli beta-galactosidase sequences, was selected on the basis that it produced blue plaques on VD60 cell monolayers under agarose overlays containing 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). F-gD beta was able to replicate normally on complementing VD60 cells. However, F-gD beta was unable to form plaques on noncomplementing Vero cells. Virions lacking gD were produced in normal amounts by Vero cells infected with F-gD beta, and the virus particles were distributed throughout the cytoplasm and on the cell surface, suggesting that gD is not essential for HSV envelopment and egress. Virions lacking gD were able to bind to cells, but were unable to initiate synthesis of viral early polypeptides. Plaque production of F-gD beta particles lacking gD was enhanced by polyethylene glycol treatment, suggesting that gD is essential for penetration of HSV into cells. Other HSV glycoproteins have been implicated in the entry of virus into cells, and thus this process appears to involve multiple interactions at the cell surface.

Guidelines for reading literature reviews.

Abstract: One strategy for dealing with the burgeoning medical literature is to rely on reviews of the literature. Although this strategy is efficient, readers may be misled if the review does not meet scientific standards. Therefore, guidelines that will help readers assess the scientific quality of the review are proposed. The guidelines focus on the definition of the question, the comprehensiveness of the search strategy, the methods of choosing and assessing the primary studies, and the methods of combining the results and reaching appropriate conclusions. Application of the guidelines will allow clinicians to spend their valuable reading time on high-quality material and to judge the validity of an author's conclusions.

Evolutionary social psychology and family homicide.

Abstract: Homicide is an extreme manifestation of interpersonal conflict with minimal reporting bias and can thus be used as a conflict "assay." Evolutionary models of social motives predict that genetic relationship will be associated with mitigation of conflict, and various analyses of homicide data support this prediction. Most "family" homicides are spousal homicides, fueled by male sexual proprietariness. In the case of parent-offspring conflict, an evolutionary model predicts variations in the risk of violence as a function of the ages, sexes, and other characteristics of protagonists, and these predictions are upheld in tests with data on infanticides, parricides, and filicides.

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

Abstract: A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained...

Game theoretic analysis of the substitutable product inventory problem with random demands

Abstract: This article uses game theoretic concepts to analyze the inventory problem with two substitutable products having random demands. It is assumed that the two decision makers (players) who make ordering decisions know the substitution rates and the demand densities for both products. Since each player's decision affects the other's single-period expected profit, game theory is used to find the order quantities when the players use a Nash strategy (i.e., they act rationally). We prove the existence and uniqueness of the Nash solution. It is also shown that when one of the players acts irrationally for the sole purpose of inflicting maximum damage on the other, the maximin strategy for the latter reduces to using the solution for the classical single-period inventory problem. We also discuss the cooperative game and prove that the players always gain if they cooperate and maximize a joint objective function.

Herpes simplex virus immunoglobulin G Fc receptor activity depends on a complex of two viral glycoproteins, gE and gI.

Abstract: Evidence was recently presented that herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) Fc receptors are composed of a complex containing a previously described glycoprotein, gE, and a novel virus-induced polypeptide, provisionally named g70 (D. C. Johnson and V. Feenstra, J. Virol. 61:2208-2216, 1987). Using a monoclonal antibody designated 3104, which recognizes g70, in conjunction with antipeptide sera and virus mutants unable to express g70 or gE, we have mapped the gene encoding g70 to the US7 open reading frame of HSV-1 adjacent to the gE gene. Therefore, g70 appears to be identical to a recently described polypeptide which was named gI (R. Longnecker, S. Chatterjee, R. J. Whitley, and B. Roizman, Proc. Natl. Acad. Sci. USA 84:147-151, 1987). Under mildly denaturing conditions, monoclonal antibody 3104 precipitated both gI and gE from extracts of HSV-1-infected cells. In addition, rabbit IgG precipitated the gE-gI complex from extracts of cells transfected with a fragment of HSV-1 DNA containing the gI, gE, and US9 genes. Cells infected with mutant viruses which were unable to express gE or gI did not bind radiolabeled IgG; however, cells coinfected with two viruses, one unable to express gE and the other unable to express gI, bound levels of IgG approaching those observed with wild-type viruses. These results further support the hypothesis that gE and gI form a complex which binds IgG by the Fc domain and that neither polypeptide alone can bind IgG.

An analysis of the hydrogen bond in BASE-HF complexes using the theory of atoms in molecules

Abstract: The nature, energetics and mechanism of BASE-HF hydrogen bonding (where BASE = OC, SC, N2, HCN, H3N, O3, SCO, CO2, N2O, SO2, H2CO, H2O, HF, H3P, H2S and HCl) are examined using the theory of atoms in molecules. The results are obtained from RHF/6-311 + +G**//6-31 G** calculations. A quantitative description of the electron redistribution and changes in atomic properties, including populations, energies, volumes and moments upon hydrogen bond formation are given by the theory, information which in turn provides a qualitative understanding of the hydrogen bond. A hydrogen bond results from the interaction of two closed-shell systems and the theory quantifies the concept of the mutual penetration of the van der Waals envelopes of the acid and base molecules. It is found that the extent of this penetration and the factors which govern it are of paramount importance in determining the strength of the interaction.

Influence of protein intake and training status on nitrogen balance and lean body mass

Abstract: The present study examined the effects of training status (endurance exercise or body building) on nitrogen balance, body composition, and urea excretion during periods of habitual and altered protein intakes. Experiments were performed on six elite bodybuilders, six elite endurance athletes, and six sedentary controls during a 10-day period of normal protein intake followed by a 10-day period of altered protein intake. The nitrogen balance data revealed that bodybuilders required 1.12 times and endurance athletes required 1.67 times more daily protein than sedentary controls. Lean body mass (density) was maintained in bodybuilders consuming 1.05 g protein.kg-1.day-1. Endurance athletes excreted more total daily urea than either bodybuilders or controls. We conclude that bodybuilders during habitual training require a daily protein intake only slightly greater than that for sedentary individuals in the maintenance of lean body mass and that endurance athletes require daily protein intakes greater than either bodybuilders or sedentary individuals to meet the needs of protein catabolism during exercise.

Problem-solving skills, solving problems and problem-based learning.

Abstract: This paper reviews the empirical evidence in support of the three concepts in the title. To the extent that a skill should be a general strategy, applicable in a variety of situations, and independent of the specific knowledge of the situation, there is little evidence that problem-solving skills, as described and measured in medical education, possess these characteristics. Instead there is an accumulation of evidence that expert problem-solving in medicine is dependent on (I) a wealth of prior specific experiences which can be used in routine solution of problems by pattern recognition processes, and (2) elaborated conceptual knowledge applicable to the occasional problematic situation. The use of problem-based learning (PBL) as an educational strategy is explored. In particular, the evidence suggesting the compatibility of PBL with this theory of expertise is discussed. Finally, I review some issues in the design of PBL curricula from the perspective of the proposed model of expertise.

A controlled trial of digoxin in congestive heart failure

Abstract: Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo. The order of treatments was determined by random allocation and patients, clinicians and research staff were blind to allocation. In patients with deteriorating condition, the treatment period was terminated and outcome measures were obtained. If deterioration occurred during the first period, the patient was crossed over without the code being broken. Seven patients required premature termination of study periods because of increasing symptoms of CHF. All 7 were taking placebo at the time (p = 0.016). Small differences in dyspnea (p = 0.044), walking test score (p = 0.055), clinical assessment of CHF (p = 0.036) and ejection fraction (p = 0.004) favored the digoxin treatment group. Patients with more severe CHF were more likely to benefit from digoxin administration. It was concluded that oral digoxin, in doses titrated to produce a serum level of 1.54 to 2.56 nmol/liter, improved quality of life and functional exercise capacity in some patients with CHF in sinus rhythm.

A clinician's guide for conducting randomized trials in individual patients

Abstract: In determining optimal treatment for a patient conventional trials of therapy are susceptible to bias. Large-scale randomized trials can provide only a partial guide and have not been or cannot be carried out for most clinical disorders. However, randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may in some circumstances provide a solution to this dilemma. In an N of 1 RCT a patient undergoes pairs of treatment periods (one period of each pair with the active drug and one with matched placebo, assigned at random); both the patient and the clinician are blind to allocation, and treatment targets are monitored. N of 1 RCTs are useful for chronic, stable conditions for which the proposed treatment, which has a rapid onset of action and ceases to act soon after it is discontinued, has shown promise in an open trial of therapy. The monitoring of treatment targets usually includes quantitative measurement of the patient's symptoms with the use of simple patient diaries or questionnaires. Pairs of treatment periods are continued until effectiveness is proved or refuted. The cooperation of a pharmacy is required for the preparation of matching placebos and conduct of the trial. Formal statistical analysis may be helpful for interpreting the results. The practical approach presented in this paper allows clinicians to conduct their own N of 1 RCTs.

Distribution of Practice in Motor Skill Acquisition: Learning and Performance Effects Reconsidered

Abstract: Recent reviews about the effects of distribution of practice in motor learning have produced quite divergent conclusions. While there is agreement that massed practice depresses performance, the effect on learning has no firm consensus. One position is that massed practice depresses learning, although there are many that argue for no learning effect. In the present paper we review this literature. When distribution is considered in terms of the length of the inter-trial interval, there is strong evidence that massed practice depresses performance and learning (when learning is assessed by absolute retention measures). This conclusion was confirmed by the results of a meta-analysis. This finding is discussed relative to other literature on distribution of practice as well as some recent issues in motor learning.

A Randomized Trial of a Family Physician Intervention for Smoking Cessation

Abstract: We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively. (JAMA1988;260:1570-1574)

Molecular cloning and expression of the major protein kinase C substrate of platelets

Abstract: In platelets, agonists that stimulate phosphoinositide turnover cause the rapid phosphorylation of a protein of apparent relative molecular mass (Mr) 40–47,000, called P47, by protein kinase C (PKC)1–4. Diverse identities have been ascribed to P47 including lipocortin5, inositol 1,4,5-trisphosphate 5-phosphomonoesterase6, pyruvate dehydrogenase α subunit7 and an actin regulatory protein8. We have isolated human P47 clones by immunological screening of a λgtll complementary DNA library from HL-60 cells, a human promyelocytic leukaemia cell line9. P47 recom-binants thus identified hybridized to a 3.0 kilobase (kb) messenger RNA in mature white blood cell lines; the same mRNA was induced in HL-60 cells during differentiation. A 1,050 base pair (bp) open reading frame that could encode a protein of Mr 40,087 was confirmed by comparison with peptide sequences from platelet P47, and by expression of the putative recombinant P47 in E. coli and in vitro. The P47 sequence appears to have been conserved throughout vertebrate evolution, and is not similar to any other known sequence including human lipocortin and the α subunit of pyruvate dehydrogenase. The P47 protein contains a potential Ca2+-binding 'EF-hand' structure and a region that strongly resembles known PKC phosphorylation sites.

Prediction of the structures of hydrogen-bonded complexes using the laplacian of the charge density

Abstract: The laplacian of the charge density is used to predict the structures and geometries of hydrogen-bonded gas-phase complexes of the type BASE-HF. The bases used are N2, OC, SC, OCO, SCO, HCN, N2O, HCP, H2O, H2S, H3N, H3P, O3, OSO, H2CO, HF, HCl, N2S and H2CS. Many of the weaker complexes have not been characterized experimentally, and so, results of full 6–31 G** geometry optimizations are presented. The laplacian of the charge density, ∇2ρ, determines where charge is locally concentrated and depleted. The point where ∇2ρ attains its maximum magnitude in a region of charge concentration in the base defines the site of electrophilic attack by the acidic H of HF. The angle of electrophilic attack predicted in this manner is compared with the ab initio equilibrium angle that the hydrogen of HF makes with the base. In general, the angles predicted using the laplacian are in good agreement with the ab initio and experimental results. The present results are also compared with those obtained from electrostatic m...

Circuit optimization: the state of the art

Abstract: The authors review the current state of the art in circuit optimization, emphasizing techniques suitable for modern microwave CAD (computer-aided design). The main thrust in the field is currently the solution of realistic design and modeling problems, addressing such concepts as physical tolerances and model uncertainties. A unified hierarchical treatment of circuit models forms the basis of the presentation. It exposes tolerance phenomena at different parameter/response levels. The concepts of design centering, tolerance assignment, and postproduction tuning in relation to yield enhancement and cost reduction suitable for integrated circuits are discussed. Suitable techniques for optimization oriented worst-case and statistical design are reviewed. A generalized l/sub p/ centering algorithm is proposed and discussed. Multicircuit optimization directed at both CAD and robust device modeling is formalized. Tuning is addressed in some detail, both at the design stage and for production alignment. State-of-the-art gradient-based nonlinear optimization methods are reviewed with emphasis given to recent, but well tested, advances in minimax, l/sub 1/, and l/sub 2/ optimization. >

Nerve growth factor promotes human hemopoietic colony growth and differentiation.

Abstract: Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been cloned. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. NGF also causes histamine release from rat peritoneal mast cells in vitro, and we have shown elsewhere that it causes significant, dose-dependent, generalized mast cell proliferation in the rat in vivo when administered neonatally. Our experiments now indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by polyclonal and monoclonal antibodies to NGF. We conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, we postulate that NGF plays an important biological role in a variety of repair processes.

Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5.

Abstract: The binding sites for the 300-, 107-, and 105-kilodalton cellular proteins which associate with human adenovirus type 5 E1A products were studied with E1A deletion mutants. All appeared to bind to the amino-terminal half of E1A products in regions necessary for oncogenic transformation. These results suggest that these cellular species may be important for the biological activity of E1A products.