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Biomedical subjects

A J Davidson

Publications and source records attributed to A J Davidson.

At least 37 records · Page 2Linked to original sources

Immunisation of cattle with recombinant acetylcholinesterase from Dictyocaulus viviparus and with adult worm ES products.

Dictyocaulus viviparus causes a serious lung disease of cattle. For over 30 years, a radiation-attenuated larval vaccine has been used with success; however, this vaccine has several disadvantages. A more stable vaccine against D. viviparus, capable of stimulating prolonged protective immunity, would be beneficial. Recent research has been directed at adult worm ES components that may be involved in parasite survival in the host. One component is the secreted enzyme, acetylcholinesterase (AChE), a target for circulating antibody in infected calves. Here, we describe a study where protection was investigated in calves immunised with either native adult ES products or a recombinant parasite AChE. These antigens were administered twice with Freund's incomplete adjuvant. Subsequently, all calves were challenged with 700 L3 and their worm burdens and immune responses compared with those in calves that received an anthelmintic-abbreviated infection and challenge control calves. Significant levels of protection were not obtained in the immunised groups but significant immunity was achieved in the calves that received the anthelmintic abbreviated infection. Antibody responses amongst the groups were different, with significantly higher IgG1 responses in the immune, infected group and in adult ES recipients. Significantly higher IgG2 responses were found in the latter group. Following challenge, the groups that received the abbreviated infection and the fusion protein produced specific antibody that bound the native enzyme. No differences were observed between groups in peripheral blood mononuclear cell responsiveness to either antigen. However, adult ES products appeared to have a mitogenic effect on these cells, whilst the fusion protein exhibited an inhibitory effect. These results suggest that in this form, AChE is not a potential vaccine candidate and that adult ES products, in contrast to previous experiments in guinea pigs, do not contain protective components.

Acetylcholinesterase↗

Food-anticipatory activity persists after olfactory bulb ablation in the rat.

Restricted daily food access acts as an entraining stimulus (zeitgeber) for a circadian clock, the feeding-entrainable oscillator (FEO). There are many properties of a daily meal that could potentially convey timing information to the FEO. Olfactory cues associated with feeding are one such property. In order to rule out olfaction as a necessary entraining stimulus, olfactory bulbectomized and sham-operated male Sprague--Dawley rats had access to food for 2 h each day. Food bin approach behavior was monitored as an index of food-anticipatory activity (FAA). Both groups entrained to the daily meal with an increase in feeder approach time several hours before meal onset. There were no significant differences in the timing or the amount of FAA between groups. Furthermore, FAA was maintained during 3 days of food deprivation in both groups. In accordance with previous studies, the results show that olfactory cues are not necessary for the entrainment of FAA.

Animals↗

Persistence of meal-entrained circadian rhythms following area postrema lesions in the rat.

Rats anticipate daily meals with increased approaches to a feeder and an increase in core body temperature. Food-anticipatory activity (FAA) is thought to be under the control of a feeding-entrained circadian oscillator (FEO). Ibotenic acid and electrolytic lesions in the region of the parabrachial nuclei (PBN) in the rat severely disrupt FAA (feeder approaches) and temperature rhythms. The PBN receive dense input from the area postrema (AP), which lacks a blood-brain barrier and thus has access to humoral factors in the systemic circulation. The present study assesses development and maintenance of FAA in rats with cautery lesions of the AP. The results demonstrate that AP lesions do not alter FAA. This experiment does not support the hypothesis that the AP in the caudal brainstem detects and relays circulating signals from the periphery that trigger FAA.

Animals↗

Use of the Bispectral Index monitor to aid titration of propofol during a drug-assisted interview.

We report two drug-assisted interviews with propofol in an 18-year-old with the diagnosis of Complex Regional Pain Syndrome type 1. We describe difficulty in titration of propofol in the first interview. Consequently, in the second interview, the Bispectral Index (BIS) monitor was applied to assist adjustment of the propofol infusion. This facilitated the achievement of a prolonged sedative-hypnotic state for a successful neuropsychological evaluation. Pertinent information was obtained from this patient. However, the role of drug-assisted interviews as a technique needs to be further elucidated.

Adolescent↗

The differences in the bispectral index between infants and children during emergence from anesthesia after circumcision surgery.

UNLABELLED: The bispectral index (BIS) correlates with consciousness during adult anesthesia. In this prospective, blinded study of children (n = 24) and infants (n = 25) undergoing elective circumcision, we evaluated BIS and consciousness level during emergence from anesthesia. Anesthesia was maintained with sevoflurane, and a penile nerve block was performed in each patient before surgical stimulation. At the completion of surgery, the sevoflurane was decreased stepwise from 0.9% in increments of 0.2%, and arousal was tested with a uniform auditory stimulus given after a steady state of end-tidal sevoflurane concentration was achieved at each step. The BIS increased significantly as the sevoflurane concentrations decreased in children (0.9%, 62.5 +/- 8.1; 0.7%, 70.8 +/- 7.4; and 0.5%, 74.1 +/- 7.1; P < 0.001 for 0.7% and 0.5% compared with 0.9%), but a similar relationship was not demonstrated in infants. The BIS values at 0.7% and 0.5% sevoflurane were significantly higher in children than infants (P < 0.02 and P < 0.002, respectively). In both children and infants, the BIS increased significantly from pre- to postarousal (children, 73.5 +/- 7 to 83.1 +/- 12, P = 0.01; infants, 67.8 +/- 10 to 85.6 +/- 13.6, P < 0.001). The BIS at which arousal was possible with the stimulus tended to be higher in children than in infants (P = 0.06). IMPLICATIONS: In this study comparing the Bispectral index (BIS) in infants and children undergoing circumcision surgery by use of a standardized surgical and anesthetic technique, a significant decrease in BIS was detected in children during a stepwise decrease in end-tidal sevoflurane concentration. A similar relationship was not demonstrated in infants less than 1 yr old. In both children and infants, BIS increased significantly from pre- to postarousal. Additional studies are necessary to determine changes in BIS with maturational changes in the electroencephalogram.

Adolescent↗

The association of foster care or kinship care with adolescent sexual behavior and first pregnancy.

OBJECTIVE: Each year more than 500 000 children enter out-of-home placement. Few outcome studies of these children specifically address high-risk sexual behavior and adolescent pregnancy. Our study investigated the relationship between living in kinship or foster care and high-risk reproductive behaviors in a nationally representative sample of women. METHODS: Data from 9620 women ages 15 to 44 years in the 1995 National Survey of Family Growth were analyzed in a cross-sectional study. Three groups-foster (n = 89), kinship (n = 513), and comparison (n = 9018)-were identified on the basis of self-reported childhood living situations. Bivariate and multiple linear regression analyses were performed. The outcome variables were age at first sexual intercourse and at first conception and the number of sexual partners. RESULTS: After adjustment for multiple predictor variables, foster care was associated with younger age at first conception (difference: 11.3 months) and having greater than the median number of sexual partners (odds ratio: 1.7, 1.0-2.8). Kinship care was associated with younger age both at first intercourse (difference = 6 months) and at first conception (difference: 8.6 months) and having greater than the median number of sexual partners (odds ratio: 1.4, 1.1-1.8). There were no differences between the kinship and foster groups. CONCLUSIONS: A history of living in either foster or kinship care is a marker for high-risk sexual behaviors, and the risk is comparable in both out-of-home living arrangements. Recognition of these risks may enable health care providers to intervene with high-risk youth to prevent early initiation of sexual intercourse and early pregnancy.

Adolescent↗

Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure.

OBJECTIVE: To determine the relative contribution of patient non-adherence, provider failure to prescribe prophylaxis, and drug failure to the continued occurrence of Pneumocystis carinii pneumonia (PCP), and to determine correlates of non-adherence. DESIGN: Retrospective case-control study. METHODS: Patients with confirmed or presumptive PCP from May 1995 to September 1997 who had at least 6 months of prior HIV care (cases) were compared to controls matched for initial CD4 cell count and date of initial HIV care. RESULTS: The incidence of PCP declined by 85% in the 28 months of the study. Of the 118 cases of PCP identified, 59 (50%) were in HIV care for > 6 months prior to PCP diagnosis. In a multivariate logistic regression model, risk factors for PCP among patients in HIV care were patient non-adherence [odds ratio (OR), 12.4; 95% confidence interval (CI), 6.4-23.5], use of prophylaxis other than trimethoprim-sulfamethoxazole (OR, 27.0; 95% CI, 13.8-52.9), and absence of antiretroviral use (OR, 7.5; 95% CI, 4.5-12.5). Provider non-adherence occurred in one out of 59 cases (2%), and five out of 106 controls (5%). Of the patients who developed PCP on prophylaxis, 18 cases (30%) appeared due to drug failure; there were no cases of apparent drug failure among patients on trimethoprim-sulfamethoxazole. In multivariate analysis, non-adherence was more common among patients of non-white race, those with a history of injecting drug use, and those with active substance abuse or psychiatric illness. CONCLUSIONS: Patient non-adherence was the most common reason for the occurrence of PCP among patients in HIV care; provider non-adherence was uncommon. Drug failure occurred only among patients on prophylaxis other than trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections↗

Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis.

The formation of hematopoietic stem cells during development occurs by a multistep process that begins with the induction of ventral mesoderm. This mesoderm is patterned during gastrulation by a bone morphogenetic protein (BMP) signaling pathway that is mediated, at least in part, by members of the Mix and Vent families of homeobox transcription factors. Following gastrulation, a subset of ventral mesoderm is specified to become hematopoietic stem cells. Key determinants of hematopoietic fate include the product of the zebrafish cloche gene and the basic helix-loop-helix transcription factor SCL. Future studies in Xenopus and zebrafish should reveal other critical factors in this developmental pathway.

Animals↗

The extent of undiagnosed HIV infection among emergency department patients: results of a blinded seroprevalence survey and a pilot HIV testing program.

This study was performed to determine the rate of previously undiagnosed HIV infection among patients presenting to an urban emergency department (ED) and to assess the feasibility of routinely offering voluntary HIV testing in this setting. HIV serostatus was determined anonymously among consecutive acute medicine and trauma ED patients (aged 18-55) who had blood drawn as part of their medical care. Excess serum was aliquoted and coded with an anonymous study code. Before performing HIV testing, the number of persons with previously reported HIV infection was determined by linkage with the state HIV/AIDS reporting registry. Concurrent with the blinded HIV serosurvey, ED patients were offered voluntary HIV testing in a pilot program. Overall, 76 of 2,155 (3.5%) adult ED patients in the blinded survey were HIV-seropositive, 15 of whom (0. 7% of those tested, 20% of those HIV-seropositive) had no infection previously reported to the state HIV/AIDS registry. In the pilot program, six of the 156 (3.8%) individuals who underwent voluntary HIV testing were HIV-seropositive, including three of 53 (5.6%) individuals without prior HIV testing. Of the six HIV-seropositive subjects, one was previously diagnosed, while five of the remaining 155 (3.2%) represented previously undiagnosed infections. Overall, 3. 5% of ED patients from whom blood was obtained for other reasons tested positive for HIV antibody, 20% of whom were previously undiagnosed. Implementation of the voluntary testing program uncovered newly diagnosed infection among 3.2% of those tested. An ED may be an important setting for routinely offering HIV testing, especially for patients who have not been previously tested for HIV.

Adolescent↗

Feeding-entrained circadian rhythms are attenuated by lesions of the parabrachial region in rats.

Rats anticipate daily restricted meals with increased approaches to a feeder and an increase in core body temperature. Food anticipatory activity (FAA) is thought to be under the control of a feeding-entrained circadian oscillator. Although numerous forebrain lesions have failed to permanently abolish FAA, the hindbrain has not been investigated. The parabrachial nuclei (PBN) integrate information from visceral and gustatory afferents. This region is also innervated by neurons in the area postrema that have access to the peripheral circulation. Therefore, it is possible that this region plays a role in triggering FAA. In two experiments, a total of 19 rats were given ibotenic acid or electrolytic lesions targeted at the PBN. The PBN-lesioned animals showed a marked attenuation in anticipatory approaches to the food bin relative to sham-operated controls. Some animals did not anticipate the meal at all. In addition, the expected increase in core body temperature was severely attenuated in the PBN-lesioned animals compared with controls. The most likely interpretation of these data is that the PBN serve as a relay for information about the zeitgeber (food in the gut) or as a clock output pathway, but not as the site of the feeding-entrained circadian oscillator.

Adaptation, Physiological↗

Plasma glucagon, glucose, insulin, and motilin in rats anticipating daily meals.

The circadian food entrainable oscillator (FEO) mediates an increase in activity preceding access to periodic meals. The FEO is anatomically independent of the suprachiasmatic nucleus (SCN), but its locus remains to be established. Whether the FEO is located in the central nervous system (CNS) or in the periphery, it seems reasonable to assume that there is a link of communication between the digestive system and the CNS because only nutritive meals entrain the FEO. Subdiaphragmatic vagotomy and visceral deafferentation with capsaicin do not eliminate food-anticipatory activity (FAA), indicating that a neural signal is not necessary. The present study investigates the hypothesis that humoral signals from the digestive system act upon the CNS to trigger or entrain FAA. Intact rats and rats with SCN lesions were entrained to daily meals and then sacrificed prior to FAA or during FAA, but before meal access. Average plasma concentrations of glucose and insulin were nearly identical in both groups. Plasma and duodenal mucosal motilin concentrations also were not different between the two times. Corticosterone was elevated during anticipation, but the difference was not statistically reliable. Glucagon concentration was decreased during FAA compared to concentration prior to FAA in both intact and SCN-lesioned subjects. This difference was not observed in control rats fasted for the same number of hours, but not previously entrained to a daily meal. Although the decrease in glucagon could be a signal that initiates FAA, a causal role remains to be established.

Animals↗

Large degenerated adrenal adenomas: radiologic-pathologic correlation.

PURPOSE: To correlate the radiologic and pathologic findings and differential diagnosis of large, degenerated adrenal adenomas. MATERIALS AND METHODS: The authors reviewed the radiologic and pathologic characteristics of 30 large adenomas with cystic regions or areas of heterogeneity that were either intrinsic or demonstrated at contrast material-enhanced computed tomography (CT) or magnetic resonance (MR) imaging. Images of 24 adrenocortical carcinomas were also reviewed to determine whether differentiating characteristics existed. RESULTS: Most of the adrenocortical adenomas were in asymptomatic women. Ten adenomas contained calcification. Pathologic examination revealed good correlation between heterogeneity and liquefied regions. Histologic examination confirmed regions of adenomatous tissue with areas of hemorrhage, amorphous degenerated material, calcification, and fibrosis. Some tumors contained myelolipomatous foci. Although some clinical and imaging findings differed between the groups, no features could be found that enabled the radiologic differentiation of adenomas from carcinomas. CONCLUSION: A subgroup of adrenal adenomas are larger, more heterogeneous, and more frequently calcified than those with the usual imaging findings. Central necrosis, hemorrhage, or both are responsible for many of the imaging features. Differentiation of these lesions from other large adrenal masses, including adrenal carcinoma, cannot be made by means of imaging alone; resection is required for the definitive diagnosis.

Adrenal Cortex↗

Feeding-entrained circadian rhythms in hypophysectomized rats with suprachiasmatic nucleus lesions.

Several pituitary hormones are important in the regulation of metabolism, and their release appears to be controlled by a circadian clock. Consequently, they may be involved in feeding-entrained circadian rhythms. Hypophysectomized (Hypox) and sham-operated male Sprague-Dawley rats had access to food for 4 h each day. Food-anticipatory activity (FAA) and core body temperature (T(b)) were monitored. Both groups entrained to the daily meal with an increase in activity in the 4 h preceding meal access and quickly reentrained after an 8-h phase advance of food access. FAA was not disrupted in either group after suprachiasmatic lesions were added. Core T(b) increased in the sham-operated subjects before mealtime, but Hypox rats failed to show this effect. Rather, T(b) declined during anticipation and throughout the food access period. Respiratory quotient (RQ), an indirect measure of metabolic rate, was measured for 24 h in some subjects. Sham-operated rats showed a dramatic downturn in RQ 1 h before mealtime, whereas Hypox rats showed a steadily decreasing RQ throughout the day. The results show that the pituitary hormones are not necessary for FAA and that in Hypox rats the anticipatory rise in T(b) and changes in RQ become dissociated from anticipatory behavior, indicating that these functions are separate outputs of the food-entrainable circadian oscillator.

Animals↗

Isolation of zebrafish gdf7 and comparative genetic mapping of genes belonging to the growth/differentiation factor 5, 6, 7 subgroup of the TGF-beta superfamily.

The Growth/differentiation factor (Gdf) 5, 6, 7 genes form a closely related subgroup belonging to the TGF-beta superfamily. In zebrafish, there are three genes that belong to the Gdf5, 6, 7 subgroup that have been named radar, dynamo, and contact. The genes radar and dynamo both encode proteins most similar to mouse GDF6. The orthologous identity of these genes on the basis of amino acid similarities has not been clear. We have identified gdf7, a fourth zebrafish gene belonging to the Gdf5, 6, 7 subgroup. To assign correct orthologies and to investigate the evolutionary relationships of the human, mouse, and zebrafish Gdf5, 6, 7 subgroup, we have compared genetic map positions of the zebrafish and mammalian genes. We have mapped zebrafish gdf7 to linkage group (LG) 17, contact to LG9, GDF6 to human chromosome (Hsa) 8 and GDF7 to Hsa2p. The radar and dynamo genes have been localized previously to LG16 and LG19, respectively. A comparison of syntenies shared among human, mouse, and zebrafish genomes indicates that gdf7 is the ortholog of mammalian GDF7/Gdf7. LG16 shares syntenic relationships with mouse chromosome (Mmu) 4, including Gdf6. Portions of LG16 and LG19 appear to be duplicate chromosomes, thus suggesting that radar and dynamo are both orthologs of Gdf6. Finally, the mapping data is consistent with contact being the zebrafish ortholog of mammalian GDF5/Gdf5.

Amino Acid Sequence↗

Glucose, but not fat, phase shifts the feeding-entrained circadian clock.

To study the ability of single macronutrients to entrain or phase shift the feeding entrainable circadian oscillator, rats with lesions of the suprachiasmatic nucleus were first maintained on a single daily meal of lab chow until robust anticipatory approaches to the feeder or anticipatory wheel running was established. The meal time was then delayed by 8 h and chow was replaced with a 25-mL solution of 0.2% saccharin or 25 mL of saccharin plus 15 g of glucose. For other phase shifts, rats received either 6 mL of vegetable oil or mineral oil for 2 consecutive days. Consumption of about 6 g (24 kcal) or more of glucose resulted in robust delaying transients on the days after ingestion, whereas saccharin induced only small delays consistent with the initiation of a free-running rhythm with a period greater than 24 h. Surprisingly, consumption of 5.5 g of vegetable oil (47 kcal) did not result in delays greater than those in rats receiving mineral oil. The introduction of oil also produced a severe reduction in approaches to the feeder which could be alleviated by placing inaccessible chow in the feeders between oil meals. Phase shifts with oil were repeated with rats housed in wheels using anticipatory wheel running as a phase marker to assess whether the lack of phase shifts with fat was apparatus dependent. As was the case with approach behavior, anticipatory wheel running was not significantly delayed by vegetable oil consumption. These results indicate that a simple monosaccharide, glucose, has zeitgeber properties for the feeding entrainable oscillator. Vegetable oil, despite a higher caloric content, may be ineffective because of slower gastric emptying and nutrient absorption or because fat is not a good zeitgeber for the feeding entrained circadian oscillator.

Animals↗

Comparison of health status, socioeconomic characteristics, and knowledge and use of HIV-related resources between HIV-infected women and men.

OBJECTIVES: The authors compared socioeconomic characteristics, and knowledge and use of human immunodeficiency virus (HIV)-related resources and health status measures between HIV-infected women and men registered within the Denver Health and Hospitals health care system. METHODS: Data collected through two Centers for Disease Control-funded surveillance initiatives (Adult Spectrum of Disease and Supplement to HIV/AIDS Surveillance) were linked. Health status measures were obtained using the Medical Outcomes Study (MOS-20) questionnaire. To compare health status measures between genders, men were matched to women based on disease stage, intravenous drug use, race, years of education, employment status, and age. RESULTS: Among all patients interviewed (n = 419), women (n = 52) were more likely to be minority, uneducated, intravenous drug users, and at earlier stages of HIV-disease than men (n = 367). Employment status was not significantly different. Knowledge of available services was generally good among both genders. Women received public assistance and had health insurance (Medicaid) more often than men. Women used support services, social work, and shelter assistance less often than men. The matched pairs analysis (n = 46 pairs) showed no significant differences between genders in physical and social function, mental health, pain, or general health perceptions; however, role function was better in women than in men (P<0.02). CONCLUSIONS: When controlling for factors that may influence health and access to health care, HIV disease generally impacts the health status of both genders similarly. Women scored higher in role function which may reflect family caretakers' responsibilities. Although knowledge of HIV-related resources was similar by gender, men made contact more often suggesting areas for enhanced outreach toward women.

Adolescent↗

Adjunctive intra-operative local anaesthesia in paediatric strabismus surgery: a randomized controlled trial.

PURPOSE: The aim of the present study was to test the hypothesis that adjunctive local anaesthesia decreases postoperative pain, vomiting or length of stay in children having strabismus repair METHOD: A prospective, randomized, triple-armed clinical trial involving a treatment comparison between topical amethocaine, sub-conjunctival bupivacaine and, as a placebo, topical normal saline was performed. All treatments were given at the end of surgery before emergence from the anaesthetic. RESULTS: Overall, there was no statistically significant difference between outcome measures in the three trial groups. Using post hoc analysis there was a statistically significant difference between the groups receiving amethocaine and bupivacaine compared with the saline group in terms of the pain score at 120 min postoperatively. This difference has little clinical significance. CONCLUSIONS: Neither topical amethocaine nor subconjunctival bupivacaine makes a clinically significant difference to postoperative pain, emesis or length of stay. Moderate dose paracetamol per rectum alone appears to be effective analgesia for strabismus surgery, although it probably masked any small adjunctive effect of the topical anaesthesia used in the present trial.

Adolescent↗

Circadian food anticipation persists in capsaicin deafferented rats.

The feeding-entrained circadian oscillator (FEO) organizes locomotor activity and other variables to anticipate daily timed meals. Whether the biological substrate for the FEO is in the central nervous system or in the periphery, there must be communication between the gut and the brain to result in a behavioral output. To investigate potential neural routes of communication, rats with suprachiasmatic lesions were given systemic capsaicin (total dose: 100 mg/kg, i.p.) to produce visceral deafferentation. Deafferentation was confirmed using the phenyl-p-benzoquinone stretch test and the corneal irritation test. A 3-h meal was made available at the same time each day while wheel running was recorded for several weeks. Results indicated that rats with capsaicin lesions were somewhat more active overall and during nonanticipation times, but the onset time and the amount of anticipatory wheel running did not differ from vehicle-treated controls. In addition, reentrainment following a phase delay of mealtime and the persistence of anticipatory activity during food deprivation were similar between the groups. Since capsaicin deafferentation and subdiaphragmatic vagotomy do not prevent food-anticipatory activity, it is likely that communication between the gut and the brain is accomplished via a humoral route.

Afferent Pathways↗