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Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 91 records · Page 5Linked to original sources

Acute pulmonary effects of ultrafine particles in rats and mice.

Ambient fine particles consist of ultrafine particles (< 100 nm) and accumulation-mode particles (approximately 100 to 1,000 nm). Our hypothesis that ultrafine particles can have adverse effects in humans is based on results of our earlier studies with particles of both sizes and on the finding that urban ultrafine particles can reach mass concentrations of 40 to 50 micrograms/m3, equivalent to number concentrations of 3 to 4 x 10(5) particles/cm3. The objectives of the exploratory studies reported here were to (1) evaluate pulmonary effects induced in rats and mice by ultrafine particles of known high toxicity (although not occurring in the ambient atmosphere) in order to obtain information on principles of ultrafine particle toxicology; (2) characterize the generation and coagulation behavior of ultrafine particles that are relevant for urban air; (3) study the influence of animals' age and disease status; and (4) evaluate copollutants as modifying factors. We used ultrafine Teflon (polytetrafluoroethylene [PTFE]*) fumes (count median diameter [CMD] approximately 18 nm) generated by heating Teflon in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity that might be helpful in understanding potential effects of ambient ultrafine particles. Teflon fumes at ultrafine particle concentrations of approximately 50 micrograms/m3 are extremely toxic to rats when inhaled for only 15 minutes. We found that neither the ultrafine Teflon particles alone when generated in argon nor the Teflon fume gas-phase constituents when generated in air were toxic after 25 minutes of exposure. Only the combination of both phases when generated in air caused high toxicity, suggesting the existence of either radicals on the particle surface or a carrier mechanism of the ultrafine particles for adsorbed gas-phase compounds. We also found rapid translocation of the ultrafine Teflon particles across the epithelium after their deposition, which appears to be an important difference from the behavior of larger particles. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-minute exposures on 3 days prior to a 15-minute exposure. This shows the importance of preexposure history in susceptibility to acute effects of ultrafine particles. Aging of the fresh Teflon fumes for 3.5 minutes led to a predicted coagulation resulting in particles greater than 100 nm that no longer caused toxicity in exposed animals. This result is consistent with greater toxicity of ultrafine particles compared with accumulation-mode particles. When establishing dose-response relationships for intratracheally instilled titanium dioxide (TiO2) particles of the size of the urban ultrafine particles (20 nm) and of the urban accumulation-mode particles (250 nm), we observed significantly greater pulmonary inflammatory response to ultrafine TiO2 in rats and mice. The greater toxicity of the ultrafine TiO2 particles correlated well with their greater surface area per mass. Ultrafine particles of carbon, platinum, iron, iron oxide, vanadium, and vanadium oxide were generated by electric spark discharge and characterized to obtain particles of environmental relevance for study. The CMD of the ultrafine carbon particles was approximately 26 nm, and that of the metal particles was 15 to 20 nm, with geometric standard deviations (GSDs) of 1.4 to 1.7. For ultrafine carbon particles, approximately 100 micrograms/m3 is equivalent to 12 x 10(6) particles/cm3. Homogeneous coagulation of these ultrafine particles in an animal exposure chamber occurred rapidly at 1 x 10(7) particles/cm3, so that particles quickly grew to sizes greater than 100 nm. Thus, controlled aging of ultrafine carbon particles allowed the generation of accumulation-mode carbon particles (due to coagulation growth) for use in comparative toxicity studies. We also developed a technique to generate ultrafine particles consisting of the stable isotope 13C by using 13C-graphite electrodes made in our laboratory from amorphous 13C powder. These particles are particularly useful tools for determining deposition efficiencies of ultrafine carbon particles in the respiratory tracts of laboratory animals and the translocation of particles to extrapulmonary sites. For compromised animals, we used acute and chronic pulmonary emphysema; a low-dose endotoxin inhalation aimed at priming target cells in the lung was also developed. Other modifying factors were age and copollutant (ozone) exposure. Exposure concentrations of the generated ultrafine particles for acute rodent inhalation studies were selected on the basis of lung doses predicted to occur in people inhaling approximately 50 micrograms/m3 urban ultrafine particles. Concentrations that achieved the same predicted lung burden per unit alveolar surface were used in rodents. (ABSTRACT TRUNCATED)

Administration, Inhalation↗

Intramolecular acid-catalyzed amide isomerization in aqueous solution.

[reaction: see text] We report for the first time that stoichiometric and even catalytic quantities of weak acids in aqueous solution can very efficiently catalyze amide isomerization in a carefully designed system in which a proton donor is situated so that intramolecular hydrogen bonding to the amide nitrogen is highly favored. Our results provide the first experimental verification that hydrogen bond donation to the amide nitrogen by charged proton donors may play a very significant role in the enzymatic catalysis of amide isomerization.

Amides↗

Physiologic and neuroendocrine responses to intravenous naloxone in subjects with Alzheimer's disease and age-matched controls.

BACKGROUND: Prior work showed that administration of naloxone HCl had different behavioral effects in patients with Alzheimer's disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous naloxone of patients with probable Alzheimer's disease to aged-matched controls. METHODS: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin were obtained at regular intervals. RESULTS: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p < .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. CONCLUSIONS: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.

Adult↗

Application of remedy studies to the development of a soil washing pilot plant that uses mineral processing technology: a practical experience.

Soil washing employing mineral processing technology to treat radionuclide-contaminated soils has been examined as a remedy alternative to the exclusive excavation, transportation, and disposal of the soil. Successful application depends on a thorough remedy study, employing a systematic tiered approach that is efficient, self-limiting, and cost effective. The study includes: (1) site and soil characterization to determine the basic mineral and physical properties of both the soil and contaminants and to identify their relative associations; (2) treatment studies to evaluate the performance of process units for contaminant separation; (3) conceptual process design to develop a treatment pilot plant; and (4) engineering design to construct, test, and optimize the actual full-scale plant. A pilot plant using soil washing technology for the treatment of radium-contaminated soil was developed, tested, and demonstrated. The plant used particle-size separation to produced a remediated product that represented approximately 50% of the contaminated soil. Subsequently, it was modified for more effective performance and application to soil with alternate characteristics; it awaits further testing. The economic analysis of soil washing using the pilot plant as a model indicates that a remedy plan based on mineral processing technology is very competitive with the traditional alternative employing excavation, transportation, and disposal exclusively, even when disposal costs are modest or when recovery of remediated soil during treatment is low. This paper reviews the tiered approach as it applies to mineral processing technology to treat radionuclide-contaminated soils and a pilot plant developed to test the soil washing process.

Cost-Benefit Analysis↗

Clinical and experimental evidence for persistent Yersinia infection in reactive arthritis.

The findings of bacterial antigens in the joint and persistent triggering infection elsewhere in the body are thought to be important in the pathogenesis of reactive arthritis (ReA). We describe a patient with clinical and laboratory features consistent with this. The initial presentation with erythema nodosum and periarthritis due to infection with Yersinia pseudotuberculosis IV was followed 13 months later by recurrent erythema nodosum with joint effusion. At that time, synovial fluid was shown to contain Yersinia antigens, and, surprisingly, Yersinia-specific 16S ribosomal RNA (rRNA) sequences were also identified by reverse transcriptase-polymerase chain reaction and sequencing. Since there was no serologic evidence of reinfection, we postulate that a silent persistent Yersinia infection was reactivated, leading to dissemination of organisms to the joint, with consequent induction of ReA. Although the finding of synovial Yersinia antigens years after the original infection in ReA has previously been reported, the presence of Yersinia 16S rRNA indicates that viable organisms were also able to reach the joint.

Antigens, Bacterial↗

Normative data and trends in quality of life from the Lung Cancer Symptom Scale (LCSS).

Normative data and trends for a disease- and site-specific quality of life (QL) instrument for individuals with lung cancer, the Lung Cancer Symptom Scale (LCSS), are presented to facilitate the user's interpretation of test scores. Data for patients enrolled in two large, identical, randomized trials of a new combination chemotherapy regimen for patients with stages III and IV non-small-cell lung cancer (NSCLC) were combined into one dataset (n = 673). For these patients with a Karnofsky performance status (KPS) of 60-100%, QL had been prospectively measured at baseline, day 29 and every 6 weeks thereafter. Descriptive statistics for the LCSS are presented for three time points (baseline, day 29 and day 71) and for specific demographic and disease-related characteristics (age, gender, race, performance status and stage of disease) to provide expected values and their variability during chemotherapy. Data from a small dataset of 63 NSCLC inpatients with KPS scores of 20-50% are also presented for a comparison sample of supportive care for inpatients and hospice patients. For the 673 NSCLC patients at baseline there were no significant differences in QL by age, gender, or race. Major presenting lung cancer symptoms at baseline for this combined sample were dyspnea 87%, cough 86%, pain 81%, loss of appetite 75%, and hemoptysis 41%. Of these patients, 81% had three or more presenting symptoms at baseline (2% had no symptoms; 5%, one symptom; 12%, two symptoms; 18%, three symptoms; 27%, four symptoms; and 36%, five symptoms). The mean LCSS baseline score (best = 0; worst = 100) was 26.56 (SD 16.10). The mean scores for day 29 and day 71 were 25.46 (SD 16.52) and 25.30 (SD 16.93), respectively, but follow-up assessments on progressers were not obtained. Stage III patients had a mean LCSS score of 23.7 (SD 15.1), whereas stage IV patients reported a mean LCSS score of 27.3 (SD 16.3). The mean LCSS score for the group with KPS 60-70% was 34.8 (SD 15.5), and that for the group with KPS 80-100% was 23.3 (SD 15.1). The mean LCSS score for the lower performance group, with KPS scores of 20-50% at baseline, was 46.85 (SD 17.65).

Adult↗

Chromosome 9 monosomy by fluorescence in situ hybridization of bladder irrigation specimens is predictive of tumor recurrence.

PURPOSE: Bladder irrigation specimens are effective for sampling the urothelium for detection of recurrent bladder cancer. These specimens can be evaluated by cytology or quantitative techniques. Proliferation and ploidy changes are readily detected using deoxyribonucleic acid (DNA) cytometry. Tumor associated chromosomal aberrations can be assayed using fluorescence in situ hybridization (FISH). The prognostic values of DNA cytometry, and chromosome 9 and 9p21 FISH on exfoliated cells from bladder irrigation specimens from 61 bladder cancer patients were evaluated. MATERIALS AND METHODS: A total of 61 consecutive bladder irrigation specimens were obtained during cystoscopy. DNA cytometry was performed by image analysis. FISH was performed using a centromeric chromosome 9 probe and a cosmid contig (COSp16) probe to the CDKN2A/p16 tumor suppressor region of 9p21. Proportional hazards regression analysis was performed with statistical software to test the predictor variables of initial patient status (presence of tumor), COSp16 fraction (the proportion of COSp16 signals relative to centromeric probe signals), monosomic and hyperdisomic fractions of the chromosome 9 probe, and hyperdiploid fraction from DNA cytometry. Median time to recurrence was calculated using statistical software survival analysis. RESULTS: Initial patient status and monosomy of chromosome 9 were predictive of bladder cancer recurrence (p <0.0001 and p = 0.0073, respectively). The 11 patients with chromosome 9 monosomy fractions greater than 15% and a visible tumor had a median time to recurrence of 105 days. In contrast, only 8 of the 25 patients with chromosome 9 monosomy fractions less than 15% and no visible tumor had recurrence within 560 days. Median time to recurrence was 185 days for 6 patients with chromosome 9 monosomy fractions greater than 15% and no visible tumor, and 225 for 19 with chromosome 9 monosomy fractions less than 15% and a visible tumor. Hyperdiploid fraction was suggestive but not predictive of bladder cancer recurrence (p = 0.078). COSp16 and hyperdisomic fractions were not predictive of bladder tumor recurrence (p = 0.11 and p = 0.30, respectively). CONCLUSIONS: Chromosome 9 monosomy by FISH was predictive of bladder tumor recurrence. Furthermore, our findings support the hypothesis that losses of tumor suppressor genes on chromosome 9 are critical, perhaps initiating genetic events in bladder cancer.

Adult↗

Hemorrhage in murine fetuses exposed to pulsed ultrasound.

In the late-gestation fetal mouse, exposure to piezoelectric lithotripter fields at amplitudes < 1 MPa produced hemorrhages in tissues near developing bone, such as the head and limbs. This study was undertaken to determine if exposure to pulsed ultrasound at diagnostic frequencies produces similar hemorrhages in the late-gestation fetal mouse. On the 18th day of gestation, fetal mice were exposed in utero to pulsed ultrasound with a 10-micros pulse duration and 100-Hz pulse repetition frequency for a total exposure duration of 3 min. Hemorrhages occurred most often to the developing fetal head. At 1.2 MHz, a threshold for hemorrhage to the fetal head was determined at positive exposure pressures of approximately 4 MPa and corresponding negative pressures of approximately 2.5 MPa. The threshold increased with at least the first power of frequency.

Animals↗

Immediate effects of a five-minute foot massage on patients in critical care.

Critical care can be considered to be a stressful environment at both physiological and psychological levels for patients. In this article, a research study in which a five-minute foot massage was offered to 25 patients (68 sessions in total) as a stress-reduction intervention is described. A quasi-experimental repeated measures design was used to collect data before, during and after the intervention. Physiological data (heart rate, mean arterial blood pressure, respirations and peripheral oxygen saturation) were obtained from the patient bedside monitoring system. Repeated measures analysis of variance indicated there was no significant effect from the intervention on peripheral oxygen saturation. However, a significant decrease in heart rate, blood pressure and respirations was observed during the foot massage intervention. Results indicated foot massage had the potential effect of increasing relaxation as evidenced by physiological changes during the brief intervention administered to critically ill patients in intensive care.

Adult↗

Physiologic and psychodynamic responses to the administration of therapeutic touch in critical care.

Recent publications have questioned the efficacy of therapeutic touch (TT). The focus of attention has been on substantiating the existence of the recipient's energy field rather than on the physiologic and psychodynamic responses to TT. In this article the physiologic and psychodynamic responses during and following the administration of TT is described. The project involved the implementation of a time series design in which the physiologic and psychodynamic responses were measured. It is acknowledged that critical care environments are stressful for patients in terms of invasive medical and nursing procedures. Continuous bright lighting, and excessive noise prohibits the potential for relaxation and sleep. Within this context, the control of confounding variables was not possible, and therefore not an object of concern in the study. Rather the responses to TT in the natural setting were of importance to discern. Statistical repeated measures analysis of variance (one way) indicated there was no significant difference between pre-, during and post-physiologic variables in response to TT. However psychodynamic responses demonstrated significant correlation's in terms of relaxation and sleep. The non significance of physiologic change in variables pre-, during and post-administration of TT indicates critically ill patients remained physiologically stable. Significant correlations of psychodynamic responses demonstrated it is possible for critically ill patients to experience periods of relaxation and sleep in an otherwise stressful environment. TT was found to be a useful therapy to enhance relaxation and sleep in critically ill patients.

Adult↗

The Caregiver Quality of Life Index-Cancer (CQOLC) scale: development and validation of an instrument to measure quality of life of the family caregiver of patients with cancer.

Family caregivers have become increasingly responsible for providing home care for cancer patients. Research has documented the distress of family caregivers; however, little has been done to evaluate the broader impact of caregiving on quality of life (QoL). The objectives of this study were to evaluate the reliability and validity of the Caregiver Quality of Life Index-Cancer (CQOLC), a new self-report instrument. Two hundred and sixty-three family caregivers of patients with lung, breast or prostate neoplasms participated. Test-retest reliability was 0.95 and internal consistency was 0.91. As expected, there were moderate correlations with overall mental health (r = 0.64), emotional distress (r = -0.50 to -0.52), burden (r = -0.65) and patient's performance status (r = -0.47) and low correlations with overall physical health (r = 0.13), social support (r = 0.22) and social desirability (r = 0.08). These results show that increased overall mental health is associated with better QoL, while more emotional distress and worsening patient performance status are associated with poorer QoL. Thus, the CQOLC appears to possess adequate validity, test-retest reliability and internal consistency. Future directions include further evaluation of sensitivity to change and factor analysis to determine the principal health-related QoL domains evaluated by the CQOLC.

Activities of Daily Living↗

DNA image cytometry in MDS bone marrow smears.

The nuclear DNA content, defined as DNA index (DI) in blasts/promyelocytes (bla/pro), were determined on Feulgen-stained bone marrow smears from 39 patients with myelodysplastic syndromes (MDS) and eight control subjects by the use of image cytometry (ICM). The DI in patients was compared to that of corresponding normal cell types, and to cytogenetic data available in 32/39 patients. The mean DI in bla/pro of patients with MDS was significantly (P < 0.01) lower compared to corresponding cell types in control subjects. By ICM, a DNA aneuploidy in bla/pro was found in 67% of the MDS patients, and 59% expressed DNA hypodiploidy. By cytogenetics, an abnormal karyotype was found in 31%, and 6/9 MDS patients with a 'hypodiploid' abnormal karyotype showed DNA hypodiploidy. Of patients with a normal karyotype (69%), seven (32%) showed a normal, 12 (55%) a lower, and three (14%) a higher DI compared to controls. No difference between groups of MDS patients was found. DNA hypodiploidy is suggested to be a common feature in MDS without a relationship to cytogenetics.

Adult↗

Psychiatric disorders in older primary care patients.

OBJECTIVE: Most older people with psychiatric disorders are never treated by mental health specialists, although they visit their primary care physicians regularly. There are no published studies describing the broad array of psychiatric disorders in such patients using validated diagnostic instruments. We therefore characterized Axis I psychiatric diagnoses among older patients seen in primary care. DESIGN: Survey of psychopathology using standardized diagnostic methods. SETTING: The private practices of three board-certified general internists, and a free-standing family medicine clinic. PARTICIPANTS: All patients aged 60 years or older who gave informed consent were eligible. MEASUREMENTS AND MAIN RESULTS: For the 224 subjects completing the study, psychiatric diagnoses were based on the Structured Clinical Interview for DSM-III-R. Point prevalence estimates used weighted averages based on the stratified sampling method. For the combined sites, 31.7% of the patients had at least one active psychiatric diagnosis. Prevalent current disorders included major depression (6.5%), minor depression (5.2%), dementia (5.0%), alcohol abuse or dependence (2. 3%), and psychotic disorders (2.0%). Dysthymic disorder and primary anxiety and somatoform disorders were less common and frequently comorbid with major depression. CONCLUSIONS: Mental disorders, particularly depression, are common among older persons seen in these primary care settings. Clinicians should be particularly vigilant about depression when evaluating older patients with anxiety or putative somatoform symptoms, given the relatively low prevalences of primary anxiety and somatoform disorders.

Aged↗

Glycaemic control, muscle glycogen and exercise performance in IDDM athletes on diets of varying carbohydrate content.

The aim of this study was to examine the effects of a high carbohydrate diet on glycaemic control, resting muscle glycogen levels and exercise performance in athletes with insulin dependent diabetes (IDDM). Seven trained (mean +/- S.D., VO2max 50.3 +/- 7.4 ml/kg/min) IDDM males consumed a high carbohydrate diet (HCD) or a normal mixed diet (NMD) for 3 week periods in a randomised crossover trial with a one week wash-out. Carbohydrate provided 59% or 50% of total energy intake, respectively, on the two diets. Fasting plasma lipids, mean blood glucose (over 96 h), fructosamine and muscle glycogen were measured and insulin use recorded. Exercise performance was evaluated by a 15 min time trial following a 50 min pre-loading block. Statistical significance was assessed using two tailed paired Student t-tests. Mean blood glucose was 10% higher on HCD than NMD (p = 0.005), fructosamine levels were 375 +/- 54 and 353 +/- 51 (mol/L on HCD and NMD, resp., p = 0.04) and daily insulin requirements were 15% higher on HCD than NMD (p = 0.02). Fasting blood lipids were similar on the two diets. Muscle glycogen was significantly lower on HCD than NMD (88.2 +/- 19.2 and 95.6 +/- 14.6 mmol/kg ww, respectively, p = 0.02). Exercise completed during the time trial was 6% less on HCD than on NMD (p = 0.007). An increased carbohydrate intake for three weeks, in IDDM athletes, is associated with a deterioration in glycaemic control, increased insulin requirements, decreased muscle glycogen and reduced exercise performance. These data do not support recommendations for IDDM athletes to consume a high carbohydrate diet, at least not when glycaemic control worsens upon following this advice, as was observed in this short-term study.

Adolescent↗

Hospice care for injection drug using AIDS patients.

Injection drug use now accounts for the majority of new AIDS cases. Treatment for these patients is both more complex and more costly than for other AIDS patients as the factors associated with drug use are obstacles to treatment. Using data from a national survey of hospices, the findings from this study indicated that resources, hospice size, years in operation, and the Medicaid waiver were associated with hospice involvement with these patients. Staff training and supports are important factors in adequately dealing with the issues that these patients present.

Acquired Immunodeficiency Syndrome↗

Effect of N(G)-nitro-L-arginine methyl ester on autonomic modulation of heart rate variability during hypovolemic shock.

OBJECTIVE: To study the changes in neuroautonomic regulation of heart rate and the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, on efferent sympathetic cardiac activity and blood pressure during hypovolemic shock. Hypotension during hypovolemic shock may be attributable, in part, to the failure of neuroautonomic regulation of heart rate and blood pressure. In addition, the release of nitric oxide may contribute to hypotension through vasodilation and inhibition of efferent sympathetic activity. DESIGN: Prospective, controlled trial. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Seventeen anesthetized adult male New Zealand White rabbits. INTERVENTIONS: The rabbits were divided into four groups: control (n = 3), control plus L-NAME (n = 5), hypovolemic (n = 4), and hypovolemic plus L-NAME (n = 5). Hypovolemic rabbits were bled of 10% of their circulating blood volume (85 mL/kg) every 10 mins until 30% cumulative hypovolemia was reached. Rabbits received either three doses of saline 1 mL/kg every 10 mins or L-NAME 10 mg/kg in 1 mL/kg of saline solution administered after each hemorrhage for a total of three doses. Changes in heart rate, respiratory rate, mean arterial pressure, plasma catecholamine levels, and heart rate power spectra were recorded every 10 mins during serial hypovolemia and during a 30-min recovery period. MEASUREMENTS AND MAIN RESULTS: During hypovolemic shock there was a decrease in log low-frequency heart rate power (p = .001) and in systolic (p = .003), diastolic (p < .001), and mean (p < .001) blood pressures compared with control rabbits. Treatment with L-NAME during hypovolemia resulted in increased log low-frequency heart rate power (p = .03) and systolic (p = .01), diastolic (p = .007), and mean (p = .009) blood pressures compared with hypovolemic rabbits who received saline placebo. CONCLUSIONS: We found that treatment with L-NAME increased efferent sympathetic cardiac activity and mean arterial pressure during hypovolemic shock compared with control rabbits. We conclude that L-NAME may blunt hypotension during hypovolemic shock by inhibiting nitric oxide synthase and may act to restore neuroautonomic cardiovascular reactivity. Spectral analysis of heart rate variability may allow for insights into the pathophysiology of shock and provide a means of monitoring the neuroautonomic cardiovascular response to therapy.

Animals↗