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In 7 patients suffering from generalized scleroderma of the acrosclerosis type, a decreased reactivity towards changes in vascular transmural pressure was observed in subcutaneous tissue of finger, as compared with arm. Clinically, the fingers were regularly found to be more severely involved in the sclerodermal process, and the pathologic microvascular responses seem to parallel the tissue pathology.
While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 microgram) from saline injected into the perifornical area of the hypothalamus (PFA), a process that took rats about 37 sessions to learn. A dose response generalization curve for PFA-injected morphine (0.01, 0.03, 0.1, and 0.17 microgram) was generated in which the two highest doses of morphine generalized to the morphine-appropriate training stimulus. Intraperitoneal (i.p.) injection of 3 mg/kg, but not 1 mg/kg morphine, resulted in morphine-appropriate responding in the PFA morphine-trained rats. A second group of rats was trained to discriminate i.p. injections of 3 mg/kg morphine from injections of saline. A dose-response generalization test for i.p.-injected morphine (0.3, 0.56, 1.0, and 1.7 mg/kg) was conducted in which the 0.17 mg/kg dose of morphine generalized to the morphine-appropriate training stimulus. Generalization tests using PFA-injected morphine doses (0.17, 0.56, 1.0, and 3.0 microgram) failed to result in morphine-appropriate responding in the i.p. morphine-trained rats. Naloxone administered into the PFA (50 microgram) or the periphery (3 mg/kg, i.p.) blocked morphine discrimination in the PFA-trained rats. However, when naloxone was injected into the PFA (50 microgram) together with i.p. morphine (3 mg/kg) in animals trained using i.p. injections, the antagonist failed to block morphine-appropriate responding. Thus, while peripheral injection of morphine generalized to the discriminative stimulus effects of morphine produced under PFA-injection training, the opposite effects were not noted.
In cohort studies the Mantel-Haenszel estimator ORMH is computed from sample data and is used as a point estimator of relative risk. Test-based confidence intervals are estimated with the help of the asymptotic chi-squared distributed MH-statistic chi 2MHS. The Mantel-extension-chi-squared is used as a test statistic for a dose-response relationship. Both test statistics--the Mantel-Haenszel-chi as well as the Mantel-extension-chi--assume homogeneity of risk across strata, which is rarely present. Also an extended nonparametric statistic, proposed by Terpstra, which is based on the Mann-Whitney-statistics assumes homogeneity of risk across strata. We have earlier defined four risk measures RRkj (k = 1,2,...,4) in the population and considered their estimates and the corresponding asymptotic distributions. In order to overcome the homogeneity assumption we use the delta-method to get "test-based" confidence intervals. Because the four risk measures RRkj are presented as functions of four weights gik we give, consequently, the asymptotic variances of these risk estimators also as functions of the weights gik in a closed form. Approximations to these variances are given. For testing a dose-response relationship we propose a new class of chi 2(1)-distributed global measures Gk and the corresponding global chi 2-test. In contrast to the Mantel-extension-chi homogeneity of risk across strata must not be assumed. These global test statistics are of the Wald type for composite hypotheses.(ABSTRACT TRUNCATED AT 250 WORDS)
The conditions of three patients who had generalized granuloma annulare responded favorably to treatment with alkylating agents. This mode of therapy in two cases was chosen on the basis of recent evidence that implicates delayed hypersensitivity mechanisms as forming part of the pathogenesis of granuloma annulare. Two patients had rapid clearing of their lesions. The response in one of these patients was observed during therapy for a concomitant plasma cell dyscrasia. The third patient had an unusual form of granuloma annulare that had evolved during a period of 28 years, with hand deformities secondary to fascial and tendon involvement and the production of contractures and lymphedema, which responded partially to therapy. The results lend further support to data implicating cellular immunity to granuloma annulare.
1. Total renal blood flow and its cortical distribution were measured by the radioactive microsphere technique in conscious rabbits and after anaethesia with pentobarbitone, chloralose-urethane or ether. 2. Pentobarbitone anaesthesia caused a fall of 26% in total renal blood flow, of 26% in superficial cortical flow, and of 24% in deep cortical flow. Sodium excretion rate fell by 33%. 3. Chloralose-urethane anaesthesia caused no change in total or regional renal blood flow, or in sodium excretion. 4. Ether anaesthesia caused an insignificant fall in total renal blood flow, but superficial cortical flow fell by 13% and deep cortical flow rose by 21%. Urinary sodium excretion fell by 65%. 5. Possible mechanisms for these changes in response to anaesthesia are discussed. 6. The effects of anaesthetic agents may influence the interpretation of published work on control mechanisms in the renal circulation.
Five young adults received audio biofeedback training to reduce trapezius EMG levels while they engaged in reading in an office, seated at a table. A multiple-baseline-across subjects design was employed in two separate studies. After training, all subjects demonstrated reduced EMG levels while reading in a home or library setting. The first study suggested that subjects reduced EMG levels by minimizing movements and altering their postures; the second study systematically demonstrated changes in such behavior, which was correlated with EMG levels. The data provide evidence that EMG biofeedback resulted in response generalization across several motoric classes, and in stimulus generalization from the training setting to the natural environment. The importance of assessing generalization is discussed.
DNA double strand breaks (DSBs) are among the most dangerous lesions that can occur in the genome of eukaryotic cells. Proper repair of chromosomal DSBs is critical for maintaining cellular viability and genomic integrity and, in multi-cellular organisms, for suppression of tumorigenesis. Thus, eukaryotic cells have evolved specialized and redundant molecular mechanisms to sense, respond to, and repair DSBs. In this chapter, we provide an overview of the progress that has been made over the last decade in elucidating the identity and function of components that participate in the cellular response to chromosomal DSBs. Then, we discuss, in more depth, the response to DSBs that occur in the context of the V(D)J recombination and IgH class switch recombination reactions that occur in cells of the lymphocyte lineage.
The total body retention (TBR) and the 5- and 24-h lumbar spine to soft tissue (LS/ST) ratios of 99mtechnetium methylene diphosphonate was studied in 19 patients with rheumatoid arthritis (RA), 16 patients with metastatic tumors that did not involve the lumbar spine, 10 patients with chronic renal failure and 17 controls. The TBR was significantly higher in all groups compared to the controls. The 5-h LS/ST did not differ between any of the groups although the 24-h LS/ST ratios were significantly elevated in RA and those with chronic renal failure. The 24-h LS/ST in RA was correlated only with disease duration. The results are consistent with a generalized increase in bone turnover in RA and may explain the recognized lack of sensitivity of quantitative scintigraphic techniques in this disorder.
The flhF gene of Pseudomonas putida, which encodes a GTP-binding protein, is part of the flagellar-motility-chemotaxis operon. Its disruption leads to a random flagellar arrangement in the mutant (MK107) and loss of directional motility in contrast to the wild type, which has polar flagella. The return of a normal flhF allele restores polar flagella and normal motility to MK107; its overexpression triples the flagellar number but does not restore directional motility. As FlhF is homologous to the receptor protein of the signal recognition particle (SRP) pathway of membrane protein translocation, this pathway may have a role in polar flagellar placement in P. putida. MK107 is also compromised in the development of the starvation-induced general stress resistance (SGSR) and effective synthesis of several starvation and exponential phase proteins. While somewhat increased protein secretion in MK107 may contribute to its SGSR impairment, the altered protein synthesis pattern also appears to have a role.
Short-form 36 (SF-36) and Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) are common instruments for measuring quality of life (QoL) in patients with knee osteoarthritis. The goal of the present study was to compare the performance of both instruments in evaluating QoL in patients with knee osteoarthritis as diagnosed by the American College of Rheumatology (ACR) criteria. Treatment included nonsteroidal anti-inflammatory drugs and patient education for 6 weeks. Face-to-face interview by an orthopaedist was done at baseline and after treatment, including collection of demographic data and use of both SF-36 and WOMAC questionnaires. Evaluation of instrument performance included reliability, validity, and responsiveness measures. Reliability was tested by analysis of internal consistency using Cronbach's alpha at baseline and after treatment. Construct validity was computed by determining the correlation between each domain of SF-36 and WOMAC (Pearson's test). Responsiveness was compared between baseline and after treatment of both SF-36 and WOMAC in each domain using the paired t test. Fifty-two patients (8 men, 48 women) with a mean age of 58.4 years were included in the present study. About 75% of subjects had less than secondary education levels and most were from agricultural communities. Sixty-four percent had mild grade knee osteoarthritis. The internal consistency of WOMAC revealed good levels of reliability, both at baseline and after treatment, in all dimensions. The reliability of SF-36 was relatively low, especially in the role physical and bodily pain dimensions (Cronbach's alpha < 0.700). Construct validity between each dimension in SF-36 and WOMAC demonstrated coefficients ranging from -0.05 to -0.409. Both WOMAC and SF-36 showed good responsiveness when comparing scores before and after treatment in all domains. In conclusion, both the Thai version WOMAC and SF-36 were valid, reliable, and sensitive to change in evaluating QoL in Thai patients with knee osteoarthritis.
Although organochlorine (OC) pesticides were replaced with organophosphates (OPs) in the early 1970s, they continue to persist in orchard environments today. Extensive research has been conducted to determine the effects of currently used OPs on cholinesterase (ChE) activity; however, although OCs continue to be prevalent in areas of previous use, few studies have looked at the toxicity of a combination of residual OC compounds with currently used OP pesticides. The focus of our study was to determine the effects of azinphos-methyl (a common OP used in apple orchards today) on ChE activity and general health in zebra finches (Taeniopygia guttata) previously exposed to p,p'-DDE (a commonly detected metabolite of DDT). The main results of our study were as follows: (1) azinphos-methyl alone caused a dose-dependent inhibition of plasma and brain ChE activity; (2) p,p'-DDE in combination with azinphos-methyl did not change azinphos-methyl inhibition of ChE activity; and (3) there were suggestions of immunostimulation in birds dosed 1 year previously to p,p'-DDE and of anemia when p,p'-DDE was combined with azinphos-methyl; however, there was no dose-response for these parameters in birds subsequently dosed with p,p'-DDE.
BACKGROUND: Research into general practitioners' responses to the changes in the health service has focused on the quantifiable dimensions of workload, stress, job satisfaction and mental health. AIM: This study set out to investigate general practitioners' practice orientations and responses to change. METHOD: The study was undertaken in 1992. 'Young principals' who had attended MSD Foundation regional courses were invited by letter to reflect on recent change in general practice and to give their views on morale and recruitment. RESULTS: Forty nine young principals responded (response rate 45%). Responses were found to cluster around four orientations to practice: collectivism, pragmatism, traditionalism, and alienation. These varied in terms of four underlying values: autonomy, individualism, external referent and optimism. CONCLUSION: General practitioners' responses to change are more complex than is currently understood and are influenced by orientation to practice. In a relatively homogeneous 'enthusiastic' subgroup of general practitioners there is striking variation in practice orientation.
This article reviews currently published works on the effects of olestra on appetite and energy intake (EI) in humans. To date 24 studies have examined the impact of olestra-containing foods on aspects of feeding behavior, which are published in 20 reports. The general response of human subjects to olestra-based decreases in dietary energy density (ED) is either poor caloric compensation or partial (nonmacronutrient specific) increases in EI. Averaging the degree of energy compensation across 22 studies gives a value of 27% (nonweighted mean). In studies where compensation occurred, fat intake but not EI was reduced. These effects appear to occur in both lean and obese, men and women and under a variety of conditions ranging from the laboratory to real life. However, all but two of these studies were short term. One study suggests that in subjects to whom weight loss is desirable these deficits can persist for up to 3 months. Subjects with no wish to lose weight may compensate better over longer periods. In another 3-month study, ingestion of olestra-based foods did not induce energy deficits but limited the significant weight gain seen on a full-fat control. The longer term effects of olestra on body weight requires further investigation. There is evidence that restrained eaters tend to eat slightly more of olestra-based foods if they know that they are reduced in fat and energy. This is probably a general response to low-fat foods rather than to olestra per se. The fact that olestra-based foods have the potential to provide the sensory qualities of real fat suggests that these foods may be particularly effective in habitual high-fat consumers with a sensory preference for dietary fat.
OBJECTIVE: To determine the variation in prevalence of common mental disorders and general practitioner (GP) responses across Australian general practices, and to identify practice characteristics that predict these rates. DESIGN: Cross-sectional national audit of general practices throughout Australia in 1998-1999. PARTICIPANTS: 46515 ambulatory care patients attending 386 GPs. MAIN OUTCOME MEASURES: Practice-based prevalence of mental disorders (based on patient-reported symptoms) and GP-reported rates of psychological diagnoses and treatment (median and range, excluding the upper and lower 10% of practices); practice characteristics (patient, doctor and organisational) that predict prevalences and rates, determined by multiple regression analysis. RESULTS: Even after omitting the upper and lower 10% of practices, there were large variations between practices in prevalence of common mental disorders (range, 39% to 59% of patients; median, 48%), and substance misuse (range, 3%-13%; median, 7%). There were also large variations between practices in rates at which GPs made psychological diagnoses in each practice (range, 12%-51%; median, 27%), judged patients to be at risk to self or others (range, 6%-54%; median, 23%), provided psychological treatments (range, 8%-41%; median, 22%) and referred patients to specialist services (range, 1%-10%; median, 4%). Practice-based rates of disorders and GP responses were predicted not only by sociodemographic characteristics of patients in each practice (eg, mean age or proportion of unemployed people), but also by doctor characteristics (eg, age and sex) and practice organisation characteristics (eg, urban versus regional or rural location). CONCLUSION: We identified patient, GP and practice characteristics that predict rates of mental disorder and treatments provided. These could be used to guide mental health service reform in general practice and assist with targeting relevant education and practice support programs.
Brain-stem auditory evoked responses (BAER) were recorded in a group of 83 patients with a diagnosis of clinically definite or probable multiple sclerosis to assess the relevance of recording contralateral responses simultaneously with ipsilateral responses and to correlate patients disability with the detection of abnormalities. The contralateral responses generally mirrored the ipsilateral responses, but in seven patients the responses differed, mainly involving the presence or absence of wave V. However, contralateral recordings did not contribute significantly to the sensitivity of lesion detection, and their main value was to aid in the recognition of waves when they were not clearly seen in the ipsilateral recordings. The BAER abnormality rates were found to be significantly correlated with disability, and it is suggested that this is an important variable to consider when undertaking or comparing results of BAER studies in patients with multiple sclerosis.
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