Biomedical subjects

B Richardson

Publications and source records attributed to B Richardson.

At least 55 records · Page 3Linked to original sources

PubMed1998

Survey of parental-leave policies and experiences in Ontario academic departments of psychiatry.

OBJECTIVE: To analyze psychiatrists' self-reports on a survey of faculty parental leaves conducted in 5 Ontario faculties of medicine. METHOD: A self-report questionnaire was mailed to all Ontario academic medical faculty members requesting information on demographics, parenting status, knowledge of parental-leave policies, personal and collegial experience of recent parental leave, and opinions about ideal parental-leave policies. RESULTS: The survey yielded a 48.6% response rate (3104 respondents). Of the respondents, 318 (10.2%) were academic psychiatrists and 113 (35.5%) of them had or adopted children since 1990. Of the 113 recent parents, 59 (53.2%) did not know their official university parental-leave policy. Fifty-one (48.1%) psychiatrists had recently taken parental leave (30 female, 21 male). Of these, females (26, 86.7%) were more likely than males (0%) to take more than 8 weeks' leave (P = 0.001). The income paid during parental leave was highly variable. Although 192 (64.4%) psychiatrists recommended that temporary replacements be hired and 175 (59.1%) recommended that the replacements be paid from a common faculty risk pool, replacements were hired for only 7 (13.7%) recent leaves. This replacement rate for psychiatry parental leaves was the second lowest of 8 medical specialties. Several leave takers felt that the leave negatively affected their research (32, 32.7%), administration (24, 23.3%), overall career course (23, 21.5%), colleagues' workload (27, 26.2), clinical work (19, 18.3%), teaching (18, 17.3%) and colleagues' attitudes toward them (11, 10.4%). Although 220 (71.5%) academic psychiatrists recommended paid leave to the primary caregiver for 16 or more weeks, 88 (28.6%) recommended less than the 17-week national standard. For secondary caregivers, 202 (66.0%) academic psychiatrists recommended a paid leave of 1-8 weeks, but 63 (20.6%) recommended paid leave for less than 1 week. One hundred and fifty-four psychiatrists (53.1%) recommended that parental-leave income be composed of usual income excluding clinical earnings, a less generous recommendation than that suggested by academic physicians in family medicine, pediatrics, internal medicine, and surgery. CONCLUSIONS: The lack of knowledge of parental-leave policies and the variability in income and duration of parental leaves among Ontario academic psychiatrists call for the development, transmission, and implementation of equitable policies. Common faculty risk pools should be established to pay temporary replacements for parental leaves to facilitate the hiring of replacements and to avoid overburdening remaining colleagues. Strategies to allow new parents to continue their career development, especially in research, need further attention. There are clear discrepancies between what psychiatrists believe to be the vital role of early parenting in child development and what they recommend and provide with regard to parental leave for their colleagues. These discrepancies become more evident when compared with the more generous policies and practices in several other medical specialties.

Academic Medical Centers↗

PubMed1998

The influence of dental unit design on percutaneous injury.

The handpiece receptacle of a European, buggy-whip-style dental unit is in a different location than that of a conventional dental unit. This study investigated whether this difference affects the incidence of percutaneous injuries among dental professionals. The researchers asked dental professionals to record descriptions of percutaneous injuries they sustained during a period of 30 workdays. Findings indicated that most injuries were bur-related and that there was no statistically significant difference between the European and the conventional dental units with respect to the incidence of percutaneous injury.

Accidents, Occupational↗

PubMed1997

Mechanisms of drug-induced lupus. III. Sex-specific differences in T cell homing may explain increased disease severity in female mice.

OBJECTIVE: To determine if sex-specific differences in lymphocyte trafficking could contribute to increased disease severity in female mice. METHODS: A lupus-like disease was induced by injecting male and female mice with procainamide-treated T cell clones. Trafficking was examined by labeling the injected cells with 51Cr or 5-chloromethylfluorescein diacetate. RESULTS: Females developed more autoimmune liver disease and greater titers of anti-DNA antibodies than did males, and 2-7 times more cells accumulated in the female spleens. Splenectomy prevented the development of autoantibodies and renal and liver disease. Oophorectomy decreased the splenic homing, autoantibody titer, and liver disease severity, to levels found in males. CONCLUSION: T cells traffic differently to the spleen in male and female mice, and the spleen appears to be essential in the disease process. This suggests that differences in T cell homing could contribute to sex-specific disease severity in this murine model, and also possibly in human disease.

Adoptive Transfer↗

PubMed1997

Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo.

OBJECTIVE: T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity. METHODS: Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo. RESULTS: Pca and Hyd were more potent than their analogs or HU in all 3 assays. CONCLUSION: The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.

Animals↗

PubMed1997

Cerebral circulatory responses of near-term ovine fetuses during sustained fetal placental embolization.

To test the hypothesis that, in response to an increase in placental vascular resistance and progressive fetal asphyxia, the changes in external carotid blood flow waveforms are directly related to changes in external carotid vascular resistance, we embolized the fetal side of the placenta in pregnant sheep and measured cerebral and external carotid artery circulatory changes in relation to changes in external carotid artery flow waveforms. Chronically catheterized fetal sheep at 0.85 of gestation were embolized (n = 11) in the descending aorta for 6 h, until fetal arterial pH fell to approximately 6.90. Fetuses became rapidly hypoxemic (P < 0.0001) and developed a mixed respiratory and metabolic acidosis (P < 0.0001 for PCO2, pH, and base excess). There was a transient 40% increase in external carotid blood flow at pH approximately 7.25 and a parallel 32% increase in fetal arterial blood pressure (both (P < 0.01), whereas the external vascular resistance remained unaltered. Cerebral blood flow increased by 130% (P < 0.0001), and cerebral vascular resistance decreased by 125% (P < 0.0001) throughout the study. The external carotid resistance index (RI) decreased by 32% (P < 0.0001) at the time external carotid vascular resistance remained unchanged. This fall in external carotid RI was due almost entirely to a 110% increase in external carotid fundamental impedance (P < 0.001). We conclude that the poor relationship between the changes in external carotid vascular resistance and RI indicated that other hemodynamic factors such as vascular impedance to pulsatile flow must be measured for correct interpretation of changes in flow waveform shape under hypoxic conditions. In addition, changes in external carotid blood flow were not proportional to changes in cerebral blood flow in this model.

Animals↗

PubMed1997

A novel limb-support system to reduce postural load in theaters.

Theatre nurses regularly stress their body when they support patients' limbs for prepping. This makes nurses vulnerable to back or upper limb pain. The Victoria Infirmary in Glasgow and the West of Scotland Department of Clinical Physics and Bio-Engineering, have developed an electrically braked limb support system to take the weight from the nurse.

Arm↗

PubMed1996

Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.

Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.

Animals↗

PubMed1996

Human placental tissue expresses a novel 22.7 kDa apolipoprotein A-I-like protein.

Since apolipoprotein A-I (apo A-I) and HDL stimulate the expression of the placental hormone human placental lactogen (hPL), experiments were performed to determine whether the human placenta synthesizes apo A-I. Western blot analysis of a partially purified extract of human term placenta with an antiserum to human apo A-I yielded an immunoreactive band with an apparent mass of approximately 23.5 kDa, which is smaller than human plasma apo A-I (28 kDa). HPLC chromatography of the partially purified placental extract on a preparative reverse-phase C-18 column yielded two fractions that reacted to the apo A-I antiserum. The mass of both fractions by mass spectral analysis was 22 721 daltons, and N-terminal amino acid sequences were identical to the first four amino acids of apo A-I (Asp, Glu, Pro, Pro). The apo A-I-like protein was not a proteolytic product of apo A-I since Northern analysis of placental RNA with a 641 bp apo A-I cDNA fragment encoding most of the 5' region of the apo A-I mRNA detected a single band of 850 nt, which is smaller than the size of apo A-I mRNA (1100 nt). Placental mRNA, however, did not hybridize with a 3' apo A-I riboprobe, indicating that the 3' region of the apo A-I-like mRNA is different from that of apo A-I mRNA. Differences in the mRNAs were confirmed by S1 nuclease analysis of placental RNA with a cDNA probe that included the 3' end of the apo A-I cDNA and by RT-PCR analysis with a series of oligonucleotide primers that span the entire cDNA for apo A-I. Since there is only a single apo A-I gene in the human genome, these findings strongly suggest that human placental tissue expresses a novel 22.7 kDa apo A-I-like protein (ALP) that results from alternative splicing of the apo A-I primary transcript.

Apolipoprotein A-I↗

PubMed1996

A methylated human 9-kb repetitive sequence on acrocentric chromosomes is homologous to a subtelomeric repeat in chimpanzees.

We have implemented an approach for the detection of DNA alterations in cancer by means of computerized analysis of end-labeled genomic fragments, separated in two dimensions. Analysis of two-dimensional patterns of neuroblastoma tumors, prepared by first digesting DNA with the methylation-sensitive restriction enzyme Not I, yielded a multicopy fragment which was detected in some tumor patterns but not in normal controls. Cloning and sequencing of the fragment, isolated from two-dimensional gels, yielded a sequence with a strong homology to a subtelomeric sequence in chimpanzees and which was previously reported to be undetectable in humans. Fluorescence in situ hybridization indicated the occurrence of this sequence in normal tissue, for the most part in the satellite regions of acrocentric chromosomes. A product containing this sequence was obtained by telomere-anchored PCR using as a primer an oligonucleotide sequence from the cloned fragment. Our data suggest demethylation of cytosines at the cloned Not I site and in neighboring DNA in some tumors, compared with normal tissue, and suggest a greater similarity between human and chimpanzee subtelomeric sequences than was previously reported.

Animals↗

PubMed1996

Demethylation of repetitive DNA sequences in neuroblastoma.

Altered genomic methylcytosine content has been described for a number of tumor types, including neuroblastoma. However, it remains to be determined for different tumor types whether specific loci or chromosomal regions are affected by a methylation change or whether the change is random. We have implemented a computer-based approach for the analysis of two-dimensional separations of human genomic restriction fragments. Through the use of methylation-sensitive restriction enzymes, methylation differences in genomic DNA between tumor and normal tissues can be detected. We report the cloning and sequencing of two fragments detectable in two-dimensional separations of genomic DNA of neuroblastomas. These fragments were found to be a part of repetitive units that exhibited demethylation in neuroblastoma relative to other tumor types. Our finding of a distinct pattern of methylation of repetitive units in neuroblastoma suggests that altered methylation at certain loci may contribute to the biology of this tumor.

Base Sequence↗

PubMed1996

Coping patterns among bone marrow transplant patients: a hermeneutical inquiry.

Bone marrow transplantation (BMT) has recently become the treatment of choice for a number of malignancies. This procedure is highly technical, involving the use of radiation and chemotherapy to destroy the patient's diseased bone marrow and with it functions of the entire immune system. It is a process with toxic effects that are experienced by all patients to varying degrees. A great deal of research related to the physiological aspects of this procedure has already been done, but considerably fewer studies have examined the psychosocial aspects of the BMT procedure from the patient's perspective. Knowledge about how BMT patients understand this process and cope with its effects is important information for nurses taking care of these patients. The purpose of the study was to describe in depth the patterns of meaning employed by patients in the hospital as they coped with the experience of their BMT. Eleven patients were interviewed from one to four times a week throughout their hospitalization. Hermeneutic analysis was used to identify five major themes: physiological functioning, alertness, attitude, social relationships, and spirituality. Implications from the findings for nursing practice are discussed.

Adaptation, Psychological↗

PubMed1996

Regional blood flow and the endocrine response to sustained hypoxemia in the preterm ovine fetus.

To determine the circulatory response of the preterm fetus to a sustained hypoxic insult, regional blood flow was measured (microsphere technique) in 12 unanesthetized fetal sheep (0.75 gestation) during a normoxic control period, after 1 h and 8 h of sustained hypoxemia, and after a 1-h recovery period. Associated endocrine changes which might relate to organ-specific changes in blood flow were also assessed. Myocardial and cerebral blood flow were increased by 240 and 90%, respectively, such that oxygen delivery to the heart was well maintained throughout the study, whereas that to the brain was significantly decreased by 8 h of hypoxic study. Regional blood flows for all structures within the brain showed similar percent increases, except that for the pituitary gland, where the increase was much smaller, and that for the choroid plexus, where blood flow actually fell. Whereas blood flow to upper body muscle showed no significant change throughout the study, that to the thyroid was increased by 70% by 1 h of hypoxic study but fell thereafter. Adrenal cortical blood flow relative to that of the medulla was increased 3-fold by 8 h of hypoxic study, indicating a differential effect of sustained hypoxia on these vascular beds. Although pituitary and thyroid blood flows showed no relationship to respective trophic and/or secretory hormones measured, values for adrenal cortical flow relative to medullary flow were well correlated with plasma concentrations of ACTH. It is concluded that the "centralization" of blood flow to vital organs in response to a sustained hypoxic insult is qualitatively similar for both the preterm and near term ovine fetus and that hypoxic regulatory mechanisms may be better protective of the heart. Additionally, a role for the functional activation of the adrenal gland in its blood flow response to sustained hypoxemia is suggested.

Acidosis↗

PubMed1996

The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression.

Studies were performed to determine whether ARP-1, which is an orphan receptor of the steroid receptor superfamily, inhibits basal activity of the human placental lactogen (hPL) promoter and the increase in hPL promoter activity in response to the receptors for thyroid hormone (TR) and retinoic acid (RAR). Co-transfection of an ARP-1 expression vector into BeWo choriocarcinoma cells, along with an expression vector containing 1.2 kb of the hPL promoter coupled to a CAT reporter gene, resulted in a dose-dependent inhibition of basal CAT activity. In addition, ARP-1 inhibited the stimulation of CAT activity by RAR alpha and TR beta expression vectors. Mobility shift assays demonstrated that ARP-1 binds specifically to a composite steroid response element on the hPL promoter that confers retinoic acid and T3 responsiveness. The results implicate an inhibitory role for ARP-1 in the regulation of hPL gene expression and strongly suggest that hPL gene expression is regulated, at least in part, by the interaction of stimulatory and inhibitory members of the steroid receptor superfamily.

Base Sequence↗

PubMed1995

The effect of naproxen on fever in patients with advanced gynecologic malignancies.

The antipyretic action of naproxen has been reported as sufficiently selective for neoplasm-related fever such that the use of this agent has been recommended to distinguish neoplastic from infectious fever. The antipyretic effect of naproxen was evaluated in gynecologic oncology patients with advanced pelvic malignancies and fever without obvious source of infection (suspected neoplastic fever). Naproxen (250 mg orally every 8 hr) was given to 12 patients with (i) a daily temperature greater than 38.3 degrees C, (ii) fever for at least 3 days, (iii) no evidence of infection on physical exam, (iv) negative results of blood and urine cultures, and (v) a chest roentgenogram negative for pneumonia. Ten of the 12 patients initially received a minimum of 3 days of empiric antibiotic therapy without resolution of fever. Within 24 hr of starting naproxen therapy, 10 patients' (83%) fever responded: Eight patients (80%) had a complete lysis of fever and two had partial lysis (20%). Temperature response was accompanied by subjective improvement in patient malaise and fatigue. Naproxen therapy was continued for 5-7 days in these patients, and chemotherapy was administered to those patients scheduled to receive it. Two patients did not respond to naproxen therapy in 24 hr; thus, it was stopped and the fever workup was continued. Of these two patients, one was eventually diagnosed with bacteremia after multiple negative blood cultures and initially no response to antibiotics. Naproxen is clinically useful in the palliation of fever-related symptoms in gynecologic oncology patients with suspected neoplastic fever. Naproxen may also allow the limitation of extensive fever workups and prolonged empiric antibiotic therapy in these patients, and prevent delays in systemic therapy or supportive care.

Adult↗

PubMed1995

Manual handling human loads in a hospital: an exploratory study to identify nurses' perceptions.

The high incident rate of musculoskeletal back problems in nursing work has long been recognized, and in many studies patient handling has been identified as a contributory factor. This paper seeks to question the application of the 'ergonomic model' for risk assessment of manual handling operations (MHO) as advocated in the MHO regulations. It describes an exploratory study, which uses a participatory approach and the qualitative analysis method of grounded theory to determine the factors perceived as important by the nurses for patient-handling tasks. The development of a model of these factors is discussed, together with the main outcome of questioning the practical benefits of dividing the generic task of patient handling into subtasks, eg bathing, for MHO risk assessment.

Journal Article↗

PubMed1995

Flow and velocity waveform indices in the ovine fetal abdominal aorta with changes in behavioural state.

The purpose of this study was to determine the extent to which flow and velocity waveform indices are comparable as measured from the ovine fetal abdominal aorta and reflect downstream vascular resistance with changes in electrocortical activity. Nine chronically catheterized fetal sheep were studied near term with continuous measurement of electrocortical activity, perfusion pressure, and fetal heart rate. A cuffed Doppler crystal and a Transonic flow probe on the descending abdominal aorta were used for the simultaneous measurement of velocity waveforms and flow waveforms, with the Resistance Index (RI), calculated for each. Mean blood flow was also obtained from the Transonic flow probe. Whereas the change in cardiovascular parameters between the low- and high-voltage electrocortical activity (ECOG) states was small, with little relationship to the change in RI measurements, across all animals there was an inverse correlation between the RI measurements and fetal heart rate, perfusion pressure and aortic blood flow during both low- and high-voltage ECOG states. The RI as measured from the velocity waveforms showed only a modest correlation to those measured from the flow waveforms. It is concluded that over the range of circulatory change generated with spontaneous change in behavioural state, the RI as measured in the abdominal aorta of the ovine fetus is primarily determined by pulsatile cardiovascular variables rather than lower body vascular resistance.

Animals↗

PubMed1995

Apolipoprotein A-I stimulates placental lactogen expression by human trophoblast cells.

Earlier studies from our laboratory indicated that apolipoprotein A-I (Apo A-I) stimulates the acute release of human placental lactogen (hPL) from trophoblast cells in culture. We have now demonstrated that Apo A-I also causes a secondary increase in hPL release, beginning about 6 h after exposure to Apo A-I, that is blocked by cycloheximide and actinomycin D. Apo A-I also stimulated a dose-dependent increase in hPL promoter activity in JAR cells transfected with a 1.1-kilobase (-1078/2) fragment of the hPL3 promoter coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. Maximal stimulation, 5.2-fold above basal levels, occurred at an Apo A-I concentration of 1.5 mg/ml, which is within the physiological concentration of Apo A-I during pregnancy. 37pA, a synthetic amphipathic peptide that mimics the secondary structure of Apo A-I and stimulates the synthesis and release of hPL, also stimulated a dose-dependent increase in CAT activity, with maximal stimulation comparable to that caused by Apo A-I. In addition, Apo A-I stimulated a modest increase in CAT activity in BeWo choriocarcinoma cells, Chinese hamster ovary cells, and HeLa cells. However, the maximal stimulation of hPL promoter activity in the Chinese hamster ovary and HeLa cells (approximately 2.5-fold above basal levels) was less than that in choriocarcinoma cells, suggesting that trophoblast cell nuclear factors may be necessary for maximal expression of the promoter in response to Apo A-I. Taken together, these results indicate that Apo A-I stimulates hPL gene expression, and that DNA elements in the first 1.1 kilobase of the promoter are sufficient for transactivation by Apo A-I.

Animals↗

PubMed1994

Lymphocyte function-associated antigen 1 overexpression and T cell autoreactivity.

OBJECTIVE: To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function-associated antigen type 1 (LFA-1) (CD11a/CD18) overexpression. METHODS: T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA-1 expression and activation requirements were examined. RESULTS: LFA-1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity. CONCLUSION: LFA-1 overexpression may contribute to T cell autoreactivity.

Azacitidine↗