De novo purine synthesis is increased in the fibroblasts of purine autism patients.
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Biomedical subjects
Publications and source records attributed to M Coleman.
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A pregnant patient at 38 weeks' gestation developed symptoms of local anaesthetic toxicity following intravenous regional anaesthesia (IVRA) for hand surgery, using a standard dose of lignocaine. Reports suggest that a number of factors, both physiological and pharmacological, combine to increase the likelihood of local anaesthetic (LA) toxicity in pregnancy despite employment of a conventional "safe" IVRA technique. It is suggested that for IVRA, pregnant patients are premedicated with a benzodiazepine, the tourniquet time is increased and the concentration of LA is decreased to reduce the risks of LA toxicity.
This paper examines stances that are being adopted in relation to the current and future direction of mental health nursing practice. The argument is made that mental health nursing is being pushed into a direction that is essentially positivistic and narrow in its focus, stating that the current hegemony of thinking which dictates that our primary focus of concern should be with individuals suffering from severe or recurring mental illness, allied with the drive towards 'evidence based practice' is symptomatic of wider issues that should be of concern to all parties interested in the issue of mental health care. The authors examine the context and rationale for these developments from socio-political, philosophical and ethical viewpoints, highlighting that their logical outcome is the exclusion of individuals from the right to health care and question the motives underpinning what could be considered a fundamental shift in the provision of mental health services. The argument is then advanced that caution should be adopted by mental health nursing services before abandoning what Gournay (1994) described as 'redundant ideologies' and that a broader view of mental health nursing action should be accommodated. The validity of trying to account for mental nursing action in quantifiable and biomechanistic terms is questioned and an alternative paradigm of accounting for such action is suggested.
We demonstrate that an irreducibly simple, uncontrolled, two-dimensional, two-link model, vaguely resembling human legs, can walk down a shallow slope, powered only by gravity. This model is the simplest special case of the passive-dynamic models pioneered by McGeer (1990a). It has two rigid massless legs hinged at the hip, a point-mass at the hip, and infinitesimal point-masses at the feet. The feet have plastic (no-slip, no-bounce) collisions with the slope surface, except during forward swinging, when geometric interference (foot scuffing) is ignored. After nondimensionalizing the governing equations, the model has only one free parameter, the ramp slope gamma. This model shows stable walking modes similar to more elaborate models, but allows some use of analytic methods to study its dynamics. The analytic calculations find initial conditions and stability estimates for period-one gait limit cycles. The model exhibits two period-one gait cycles, one of which is stable when 0 < gamma < 0.015 rad. With increasing gamma, stable cycles of higher periods appear, and the walking-like motions apparently become chaotic through a sequence of period doublings. Scaling laws for the model predict that walking speed is proportional to stance angle, stance angle is proportional to gamma 1/3, and that the gravitational power used is proportional to v4 where v is the velocity along the slope.
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This study explores how granddaughters account for the development of their relationships with their maternal grandmothers. The retrospective interviewing technique was used to elicit turning points in their relational histories. Analysis of the turning point content revealed several different types of turning points that reflected both normative and idiosyncratic events. Increases in relational closeness resulted from decreases in geographic separation, engaging in shared activities, deaths or serious illnesses in the family, and family disruptions. Decreases in closeness were associated with negative experiences with the grandmother, increases in geographic separation, and the transition to college. Granddaughters reported that turning points related to death or serious illness and participation in shared activities were the most significant ones in their relationships with maternal grandmothers.
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Procedures of sampling and measurement contribute variability and uncertainty to exposure models that predict incidence and levels of organisms in food products. This paper focuses on methods that account for sampling and measurement error in fitting distributions of organisms in food products for use in exposure models for microbial risk assessment. Define y to be a measured density on a sample selected with stipulated probability from a population, and define x to be the "true" density for that sample. Designate the conditional distribution of y given the sample with "true" value x as g(y/x), and let F(x) be the unknown cumulative density of x. The distribution of the observed values y, h(y), can be expressed through the integral equation h(y) = integral of g(y/x) dF(x). Knowledge of g(y/x) and h(y) enables an estimate of the unknown distribution of the organism's F(x). In applications to risk assessment, use of continuous distributions described by a few parameters is desirable. Also desirable may be imputation or assignment of possible nonzero values for nondetect observations--those results below the limit of detection of the methodology--that may not be truly zero. This paper explores the use of the above formulation for estimating distributions of organisms used for microbial risk assessment and presents some simple examples.
Great uncertainty exists in conducting dose-response assessment for microbial pathogens. The data to support quantitative modeling of dose-response relationships are meager. Our philosophy in developing methodology to conduct microbial risk assessments has been to rely on data analysis and formal inferencing from the available data in constructing dose-response and exposure models. The probability of illness is a complex function of factors associated with the disease triangle: the host, the pathogen, and the environment including the food vehicle and indigenous microbial competitors. The epidemiological triangle and interactions between the components of the triangle are used to illustrate key issues in dose-response modeling that impact the estimation of risk and attendant uncertainty. Distinguishing between uncertainty (what is unknown) and variability (heterogeneity) is crucial in risk assessment. Uncertainty includes components that are associated with (i) parameter estimation for a given assumed model, and (ii) the unknown "true" model form among many plausible alternatives such as the exponential, Beta-Poisson, probit, logistic, and Gompertz. Uncertainty may be grossly understated if plausible alternative models are not tested in the analysis. Examples are presented of the impact of variability and uncertainty on species, strain, or serotype of microbial pathogens; variability in human response to administered doses of pathogens; and effects of threshold and nonthreshold models. Some discussion of the usefulness and limitations of epidemiological data is presented. Criteria for development of surrogate dose-response models are proposed for pathogens for which human data are lacking. Alternative dose-response models which consider biological plausibility are presented for predicting the probability of illness.
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What are the species boundaries of face processing? Using a face-feature morphing algorithm, image series intermediate between human, monkey (macaque), and bovine faces were constructed. Forced-choice judgement of these images showed sharply bounded categories for upright face images of each species. These predicted the perceptual discrimination boundaries for upright monkey-cow and cow-human images, but not human-monkey images. Species categories were also well-judged for inverted face images, but these did not give sharpened discrimination (categorical perception) at the category boundaries. While categorical species judgements are made reliably, only the distinction between primate faces and cow faces appears to be categorically perceived, and only in upright faces. One inference is that humans may judge monkey faces in terms of human characteristics, albeit distinctive ones.
Recent evidence has shown that insulin-like growth factor-I (IGF-I) plays an important role in the development, maintenance, and regeneration of peripheral nerves and skeletal muscle. IGF-I offers the potential to treat neuromuscular diseases in humans. We have developed a nonviral gene therapy method to express and produce localized and sustained therapeutic levels of IGF-I within target muscles by intramuscular injection of formulated plasmids. The purpose of the present study was to demonstrate that intramuscular injection of a plasmid encoding human IGF-I (hIGF-I) and engineered to restrict expression to skeletal muscle produces sustained local concentrations of biologically active hIGF-I. Normal rats received a single intramuscular injection of plasmids formulated as a complex with polyvinylpyrrolidone (PVP). Results show that hIGF-I mRNA and hIGF-I protein were detectable in the injected muscles for the duration of the study (28 days), whereas the hIGF-I protein was not detected in blood. Biological activity of hIGF-I was determined by immunodetection of a nerve-specific growth-associated protein, GAP-43, an indicator of motor neuron sprouting. Placement of human growth hormone (hGH) 3' untranslated region enhanced GAP-43 staining, probably due to improved secretion of hIGF-I. Enhanced immunoreactivity of GAP-43 was observed in muscles injected with the formulated hIGF-I plasmid when compared to controls. These results demonstrate that intramuscular injection of hIGF-I plasmid formulated as a complex with PVP produces a localized and sustained level of biologically active hIGF-I.
Autism is a heterogeneous condition and the possible pathogenic role of several different factors has been postulated. Association between celiac disease and neurological manifestations such as drug resistant epilepsy and cerebral calcifications is well known. Some authors in the past also reported the existence of a linkage with autism. On the basis of these observations, we have evaluated 120 patients with celiac disease diagnosed at the Pediatric Clinic of the University of Catania, Italy, in order to identify behavioral problems and autistic features: there were 20 controls for this part of the study. At the same time, AGA and AEMAb were assayed in 11 patients with infantile autism and 11 age- and sex-matched controls. No celiac case was detected among the group of autistic patients and, although two of them had slightly increased levels of AGA IgG and AEMAb, subsequent antibodies determinations and jejunal biopsies gave normal results. Moreover none of the celiac patients had a positive DSM-III-R test for infantile autism.
Bacteriorhodopsin (bR) functions as a light-driven proton pump in the purple membrane of Halobacterium salinarium. A major feature of bR is the existence of an active site which includes a retinylidene Schiff base and amino acid residues Asp-85, Asp-212, and Arg-82. This active site participates in proton transfers and regulates the visible absorption of bacteriorhodopsin and its photointermediates. In this work we find evidence that Thr-89 also participates in this active site. The substitution Thr-89 --> Asn (T89N) results in changes in the properties of the all-trans retinylidene chromophore of light-adapted bR including a redshift of the visible lambda(max) and a downshift in C=N and C=C stretch frequencies. Changes are also found in the M and N intermediates of the T89N photocycle including shifts in lambda(max), a downshift of the Asp-85 carboxylic acid C=O stretch frequency by 10 cm(-1), and a 3-5-fold decrease in the rate of formation of the M intermediate. In contrast, the properties of the 13-cis retinylidene chromophore of dark-adapted T89N as well as the K and L intermediates of the T89N photocycle are similar to the wild-type bacteriorhodopsin. These results are consistent with an interaction of the hydroxyl group of Thr-89 with the protonated Schiff base of light-adapted bR and possibly the N intermediate but not the 13-cis chromophore of dark-adapted bR or the K and L intermediates. Thr-89 also appears to influence the rate of Schiff base proton transfer to Asp-85 during formation of the M intermediate, possibly through an interaction with Asp-85. In contrast, the hydroxyl group of Thr-89 is not obligatory for proton transfer from Asp-96 to the Schiff base during formation of the N intermediate.
The purpose of this study was to investigate the effects of family structure information on how nurses (a) interpreted information, (b) gathered data, and (c) responded to a patient. Nurses were randomly assigned to see one of eight videotaped interviews portraying: married mother, married with no children, divorced mother, divorced with no children, unmarried mother, unmarried with no children, remarried with spouse's children (stepmother), and remarried with no children. The results indicate that the technical aspects of nursing may be affected only in a relatively minor way, but the affective dimensions of nursing care may be more detrimentally influenced by knowing about a patient's family structure.
In rats, copper deficiency leads to low copper metalloenzyme activity, high serum cholesterol, and cardiovascular lesions. In humans, moderately low copper intake may be common, but the consequences remain largely uncertain. The present study examined the effects of copper supplementation (2 mg/d for 4 weeks in a copper/placebo crossover design) in 20 adult men with moderately high plasma cholesterol. End-point measurements were three copper enzyme activities, erythrocyte superoxide dismutase (SOD), plasma ceruloplasmin (Cp), and plasma diamine oxidase (DAO), and three parameters related to the risk of cardiovascular disease (CVD), plasma cholesterol, plasma lipoprotein (a) [Lp(a)], and lag times for very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) oxidation in vitro. Although copper had no significant effects on any parameter for the entire study group, it did significantly increase two enzyme activities (SOD and DAO), as well as lipoprotein oxidation lag times, in 10 subjects in the lower half of a median split for precopper values. Thus, copper supplementation appeared to influence some types of measurements in subjects beginning with less than median values.
A complementary DNA (cDNA) clone encoding chicken insulin-like growth factor binding protein-5 (cIGFBP-5) was isolated. The nucleotide sequence of the 1236-bp clone encodes a mature polypeptide of 251 amino acids with a calculated molecular weight of approximately 28.2 kDa. The deduced amino acid sequence is 83% identical to human IGFBP-5. Labeled cIGFBP-5 cDNA detected a single mRNA transcript of approximately 6 kb by Northern blot analysis of various tissues obtained from embryonic and 6 weeks post-hatch chickens; interestingly, adult heart showed an approximately 10-fold increase in cIGFBP-5 mRNA relative to embryonic heart. The pattern of IGFBP-5 mRNA expression in chicken tissues was similar to that found in mammals during fetal and extrauterine life. In addition, IGFBP-5 mRNA was abundant in primary cultures of chicken myoblasts throughout in vitro differentiation and fusion. The conservation of IGFBP-5 primary structure and expression pattern across vertebrate species suggests conservation of important functions during evolution, particularly in muscle differentiation.
To evaluate a strategy of one cycle of dose-intensive chemotherapy for patients with Hodgkin's disease in sensitive relapse and two cycles for those with refractory disease, 122 patients received dose-intensive chemotherapy followed by autotransplant in two consecutive studies. Patients with refractory disease were offered a second transplant with different conditioning in the absence of progression or excessive toxicity. CR was present after treatment in 46% while 16% died in the peritransplant period. Of 41 patients with primary refractory disease and 42 with refractory relapse, 24 and 21 respectively received a second cycle. Of these 45 refractory patients, 12 were in CR and 11 in PR after the first cycle and 10 of these 11 in PR achieved a durable CR with the second transplant. The CR rate is 37% in patients with refractory relapse and 19% in those with primary refractory disease. At a median follow-up of 4 years, median survival is 45 months. Progression-free survival of the refractory patients who could receive a second cycle was similar to that of patients with sensitive disease. A sequential transplant strategy is feasible. A subgroup of patients with refractory disease can achieve long-term survival after sequential BMT.