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Biomedical subjects

C A Smith

Publications and source records attributed to C A Smith.

At least 253 records · Page 14Linked to original sources

On babies and bathwater: disease impact and negative affectivity in the self-reports of persons with rheumatoid arthritis.

The degree to which self-reports of health and functioning reflect negativity (NA), a dispositional tendency to emphasize the negative, was examined with data from a 7-year longitudinal study of adaptation to rheumatoid arthritis. Principal component analyses performed on each of 8 waves of data consistently indicated that the dominant factor in these data was defined by measures of pain and functional impairment. In the final wave, Disease Impact, a scale derived from this component, was directly compared to NA. The 2 scales demonstrated considerable discriminant validity, and most of the significant intercorrelations among Disease Impact and the other variables examined remained statistically significant after the influence of NA was partialed out. These results suggest that reports of pain, impairment, and associated variables reflected disease-related outcomes and processes and not simply NA.

Activities of Daily Living↗

Arthritis and perceptions of quality of life: an examination of positive and negative affect in rheumatoid arthritis patients.

The utility of measuring both positive and negative affective states for assessing rheumatoid arthritis (RA) patients was examined in 3 independent samples of male and female RA patients (Sample A: 179 women, 48 men; Sample B: 177 women, 24 men; Sample C: 134 women, 38 men). Confirmatory factor analyses of each sample indicated that positive and negative affect constituted separate, negatively correlated factors. The relations among disease variables, coping, and affects were consistent with a model in which coping mediates the relationship between disease variables and positive and negative affect. Patients with higher pain and limitation from RA had higher levels of maladaptive coping, and maladaptive coping was associated with lower positive affect and higher negative affect. Those RAs with higher activity limitation also reported less adaptive coping, which was associated with less positive affect.

Activities of Daily Living↗

Production of genetically modified Epstein-Barr virus-specific cytotoxic T cells for adoptive transfer to patients at high risk of EBV-associated lymphoproliferative disease.

EBV-induced lymphoproliferative disease (EBV-LPD) is a disorder most commonly associated with the immunocompromise that follows allogeneic organ transplantation. In patients receiving T cell-depleted bone marrow from HLA-mismatched or HLA-matched unrelated donors, the incidence of EBV-LPD is particularly high, ranging from 5 to 30%. Administration of EBV-specific cytotoxic T lymphocytes may be one means of preventing and treating this disease. We now describe a method that allows the routine and timely preparation of large numbers of such cells to allow their safe administration to bone marrow transplant recipients. We also describe how these cells may be genetically marked before infusion, to determine their fate and disposition in vivo.

Adolescent↗

The development and validation of the Perceived Health Competence Scale.

A sense of competence or self-efficacy is associated with many positive outcomes, particularly in the area of health behavior. A measure of a sense of competence in the domain of health behavior has not been developed. Most measures are either general measures of a general sense of self-efficacy or are very specific to a particular health behavior. The Perceived Health Competence Scale (PHCS), a domain-specific measure of the degree to which an individual feels capable of effectively managing his or her health outcomes, was developed to provide a measure of perceived competence at an intermediate level of specificity. Five studies using three different types of samples (students, adults and persons with a chronic illness) provide evidence for the reliability and validity of the PHCS. The eight items of the PHCS combine both outcome and behavioral expectancies. Results from the five studies indicate that the scale has good internal consistency and test-retest reliability. The construct validity of the scale is demonstrated through the support obtained for substantive hypotheses regarding the correlates of perceived health competence, such as health behavior intentions, general sense of competence and health locus of control.

Adaptation, Psychological↗

Evidence for a role of cytochrome P450 2D6 and 3A4 in ethylmorphine metabolism.

Ethylmorphine is metabolised by N-demethylation (to norethylmorphine) and by O-deethylation (to morphine). The O-deethylation reaction was previously shown in vivo to co-segregate with the O-demethylation of dextromethorphan indicating that ethylmorphine is a substrate of polymorphic cytochrome P450(CYP)2D6. To study further the features of ethylmorphine metabolism we investigated its N-demethylation and O-deethylation in human liver microsomes from eight extensive (EM) and one poor metaboliser (PM) of dextromethorphan. Whereas N-demethylation varied only two-fold there was a 4.3-fold variation in the O-deethylation of ethylmorphine, the lowest rate being observed in the PM. Quinidine, at a concentration of 1 microM, inhibited O-deethylation in microsomes from an EM, but was unable to do so in microsomes from the PM. The immunoidentified CYP2D6 and CYP3A4 correlated with the rates of O-deethylation (r = 0.972) and N-demethylation (r = 0.969), respectively. We conclude that the O-deethylation of ethylmorphine is catalysed by the CYP2D6 in human liver microsomes consistent with previous findings in healthy volunteers.

Adult↗

Estimating multipoint recombination fractions.

The likelihood in linkage investigations can be expressed as a polynomial in the relevant recombination fractions. With polymorphic characters, this can be reduced to a product of separate factors for female and male recombinations, with only mild loss of information. With three generation data the polynomials take a specially simple form. Algorithms are given for finding maximum likelihood estimates and their standard errors.

Female↗

Association between the CYP1A1 gene polymorphism and susceptibility to emphysema and lung cancer.

Aim-To investigate cytochrome P4501A1 (CYP1A1) polymorphism and susceptibility to emphysema and lung cancer.Methods-A novel polymerase chain reaction (PCR) for genotyping the CYP1A1 polymorphism, corresponding to putative low or high enzyme activity, was developed to genotype lung cancer resection samples which had been assessed macroscopically for the presence of centriacinar and panacinar emphysema. Samples were collected and genotyped from a group of patients with chronic obstructive airways disease. A control group of anonymous blood donations was genotyped to determine the basal levels of the polymorphism in the Scottish population.Results-The high activity allele of the CYP1A1 gene is associated with susceptibility to centriacinar emphysema and lung cancer but not panacinar emphysema. CYP1A1 polymorphism is not linked to lung cancer in the absence of emphysema, nor to chronic obstructive airways disease which is the clinical manifestation of emphysema, particularly of the panacinar type.Conclusions-Susceptibility to emphysema and lung cancer is associated with polymorphism of the P4501A1 gene. A trend towards damage of centriacinar pattern has been detected, which supports the theory that centriacinar emphysema results from local, direct damage to the respiratory bronchioles from exposure to cigarette smoke.

Journal Article↗

Diastolic time: an important determinant of regional arterial blood flow.

In unanesthetized dogs we measured heart rate, blood pressure, and external iliac, celiac, and renal artery flows on a beat-by-beat basis. All three flows fluctuated in synchrony with breathing. Although the fluctuations in renal flow could to a large degree be explained by fluctuations in blood pressure, this was not the case in the external iliac artery where flow increased when pressure decreased and decreased when pressure increased. These paradoxical fluctuations in flow appear to be caused by respiratory fluctuations in heart rate, since we observed a strong (r = 0.89) correlation between external iliac flow and the length of the preceding diastole. Single long diastolic periods, induced by atropine, were always followed by a beat of increased flow even though arterial pressure was constant. We conclude that diastolic time has a profound impact on blood flow during the next beat. Our data support a model of the arterial system in which backpressure to flow through a bed is dependent on the amount of time for diastolic runoff into the capillaries.

Animals↗

Respiratory and cardiovascular responses to increased and decreased carotid sinus pressure in sleeping dogs.

The purpose of this study was to determine the effects of changing blood pressure in the carotid sinus (Pcs) on ventilatory output during wakefulness and non-rapid-eye-movement sleep in unanesthetized dogs. Eight dogs were chronically instrumented so that ventilation, heart rate, and blood pressure could be measured while pressure in the isolated carotid sinus was rapidly changed by means of an extracorporeal perfusion circuit. Raising Pcs 35-75 mmHg consistently reduced ventilation 15-40% in a dose-response fashion, with little or no further diminution in minute ventilation as Pcs was further increased > 75 mmHg above control level. This decrease in minute ventilation was immediate, due primarily to a decrease in tidal volume, and was sustained over the 20-s period of elevated Pcs. Increases in Pcs also caused immediate sustained reductions in systemic blood pressure and heart rate, both of which also fell in a dose-dependent fashion. The ventilatory and systemic cardiovascular responses to increased Pcs were the same during wakefulness and non-rapid-eye-movement sleep. Decreasing Pcs 40-80 mmHg caused a sudden carotid chemoreceptor-mediated hyperpnea that was eliminated by hyperoxia. We conclude that increasing Pcs causes a reflex inhibition of ventilation and that this reflex may play a role in sleep-disordered breathing.

Animals↗

Effects of raising carotid sinus pressure on upper airway resistance and EEG frequency in sleeping dogs.

The purpose of this study was to determine whether acutely raising carotid sinus pressure (Pcs) causes changes in upper airway resistance and/or electroencephalographic (EEG) frequency during wakefulness and non-rapid-eye-movement (NREM) sleep. Five dogs were chronically instrumented so that breathing, tracheal pressure, mouth pressure, EEG, and electrooculogram could be measured while pressure in the vascularly isolated carotid sinus was rapidly increased between 40 and 150 mmHg via an extracorporeal perfusion circuit. Dogs were studied during both wakefulness and NREM sleep. Multiple trials of increased Pcs were conducted in each dog. We observed that increasing Pcs 40-150 mmHg caused not only a reflex cardiovascular response but also a 15-40% decrease in minute ventilation. Raising Pcs caused no physiologically significant changes in upper airway resistance over the range of airway pressures and flow rates encountered during inspiration and expiration. Even dogs that demonstrated moderate to substantial sleep-induced increases in airway resistance did not consistently increase resistance during superimposed baroreceptor stimulation. Small increases in airway resistance were sometimes observed during baroreceptor stimulation, but this was not a consistent finding. Acute increases in Pcs did not cause measurable changes in EEG frequency during wakefulness or NREM sleep. We conclude that acute stimulation of the carotid sinus baroreceptors does not cause physiologically meaningful changes in upper airway resistance or EEG activity in awake or sleeping dogs.

Airway Resistance↗

Ventilatory effects of specific carotid body hypocapnia in dogs during wakefulness and sleep.

We used extracorporeal perfusion of the vascularly isolated carotid sinus region to determine the effects of specific carotid body chemoreceptor hypocapnia-alkalosis on ventilatory control in the unanesthetized dog. Eight female dogs were studied during wakefulness, non-rapid-eye-movement (NREM) sleep, and rapid eye movement (REM) sleep. Carotid body perfusions lasted from 1 to 2 min, and each trial was preceded by a 1-min control period. Two levels of carotid body hypocapnia were employed, approximately 7 and 14 Torr below eupneic levels in a given dog. We found that 1) During wakefulness and NREM sleep, carotid body hypocapnia caused reduced tidal volume (VT) but not apnea or expiratory time prolongation. 2) The inhibition of ventilation in response to carotid body hypocapnia was graded below normocapnia, showing the highest sensitivity at carotid body PCO2 near 7 Torr below eupneic values. Inhibition reached a maximum near 14 Torr below the eupneic level; VT, inspiratory minute ventilation (VI), and VT-to-inspiratory time ratio fell 31, 23, and 27% in wakefulness and 30, 23, and 30% in NREM sleep. 3) Reductions in ventilation in response to carotid body hypocapnia are lessened but still persist throughout perfusion (up to at least 130 s) despite significant systemic hypercapnia. 4) During REM sleep, carotid body hypocapnia had no consistent inhibitory effect on ventilation until carotid body PCO2 was reduced to values near 14 Torr below the eupneic level, at which point ventilation was similar to wakefulness and NREM. 5) Moderate carotid body hypocapnia was as effective as carotid body hyperoxia in reducing VT and VI. We conclude that carotid body hypocapnia-alkalosis can significantly inhibit eupneic VT and ventilation during wakefulness and NREM sleep and, if the hypocapnia is severe enough, during REM sleep.

Animals↗

The lived experience of staying healthy in rural African American families.

Decreased government spending for public health programs and increased government expectations that consumers should take responsibility for self-care and health promotion activities are current trends (Lee & Estes, 1990; Naisbitt, 1984). The purpose of this study was to reveal through phenomenological analysis the meaning of staying healthy for the participants. Staying healthy emerged as a dynamic response to life events that involved activity and relatedness in synchrony with life's rules and emotional tranquility. The findings confirm that phenomenological research can reveal the meaning of health within the context of culture and support the conceptualization of health as a developmental process for African American families.

Adaptation, Psychological↗

Alendronate treatment of naturally-occurring periodontitis in beagle dogs.

The treatment of periodontal disease has been largely directed at the microbiological etiology. The prevention of bone loss by modulating the host response to the bacteria may be a useful adjunctive method in the management of periodontitis. Alendronate, an amino bisphosphonate, may inhibit bone loss in osteolytic diseases by altering osteoclast activity. The objective of this double-blind study was to evaluate alendronate inhibition of alveolar bone loss in the naturally occurring beagle dog model of periodontitis. Sixteen 7 to 9 year old beagles with moderate-to-severe periodontitis were studied for 6 months. The dogs were stratified into two groups based on initial periodontal severity. One group received 3.0 mg/kg alendronate weekly orally and the other group received a placebo. Silk ligatures were placed on the study teeth for the first 3 months of the study to exacerbate the periodontal destruction. Clinical data were collected for attachment level, gingival index, plaque index, and mobility at baseline and one-month intervals. Intraoral radiographs were made at baseline and at 3 and 6 months. The mandibles were processed for histology at month 6. The radiographs were analyzed by digital image analysis of the subtracted images. A statistically significant difference in bone mass (P < 0.001) was observed between the alendronate and placebo groups. The bisphosphonate had no effect on the clinical parameters of gingival inflammation or plaque. A trend toward decreased attachment loss and mobility was observed in favor of the alendronate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗

Polymorphisms in drug-metabolizing enzymes as modifiers of cancer risk.

The identification of low-penetrance genes, the polymorphisms of which increase an individual's risk of developing cancer, are likely to be extremely important in the general population. In this report we analyzed two genes involved in detoxification. In a number of loci, we identified polymorphic variation correlating with the expression of the gene product. We analyzed two such loci, the cytochrome P-450 gene CYP2D6 and the N-acetyltransferase 2 (NAT2) genes, in patients with bladder and colon cancer, respectively. We observed no statistically significant associations between the control and cancer populations; however, there was a small increase in heterozygote number in bladder cancer.

Arylamine N-Acetyltransferase↗