Search PubMed⌕ Search

Biomedical subjects

R Bland

Publications and source records attributed to R Bland.

At least 37 records · Page 2Linked to original sources

Thyroid hormone, vitamin D and retinoid receptor expression and signalling in primary cultures of rat osteoblastic and immortalised osteosarcoma cells.

3,5,3'-Tri-iodothyronine (T3), 1 alpha,25(OH)2-vitamin D3 (D3) and retinoids activate related nuclear receptors which interact by heterodimerisation to regulate gene expression. Actions of each hormone are discrete and may be specified by changes in the relative concentrations of their receptors (T3R, vitamin D receptor (VDR), retinoic acid receptor (RAR), retinoid X receptor (RXR)). T3, D3 and retinoids are essential for skeletal development and maintenance and we have previously shown complex interactions amongst their signalling pathways in osteosarcoma cells. In these studies we demonstrate that similar T3R, VDR, RAR and RXR proteins are co-expressed in both osteoblast lineage cell primary cultures and osteosarcoma cells by Western blotting. We investigated whether hormone interactions in bone result from changes in receptor stoichiometry. Cells were treated with combinations of T3, D3, 9-cis retinoic acid (9-cis RA) and all-trans retinoic acid (RA) that are known from previous studies to produce complex cell specific responses. No alteration in expression of any receptor protein was seen in response to any hormone combination in three phenotypically distinct osteosarcoma cell lines. Thus, in contrast to studies of overexpressed receptors in vitro, changes in the physiological concentrations of endogenous T3R, VDR, RAR and RXR do not specify discrete hormone actions in osteoblastic cells. Other unidentified factors are likely to modulate hormone action in these bone cells.

Animals↗

Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults.

The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder.

Adult↗

Psychiatric manifestations of multiple sclerosis: a review.

OBJECTIVE: To report the occurrence, type, causes, and management of psychiatric manifestations in multiple sclerosis (MS). METHOD: Review of recent, relevant literature. RESULTS: Psychiatric illness, especially depression, occurs much more frequently than expected in patients with MS, is frequently unrecognized or ignored, and is treatable using standard methods, although patients with MS may be unusually sensitive to side effects of tricyclic antidepressants. CONCLUSIONS: Research is needed to better define the causes of psychiatric syndromes in patients with MS. Those treating MS should increase their awareness of and sensitivity to the likelihood of psychiatric disorder in these patients.

Adaptation, Psychological↗

Investigating discharge destinations for schizophrenic patients.

An audit of hospital records of 542 patients diagnosed as having schizophrenia discharged in the years 1986-88 from the Princess Alexandra Hospital, Brisbane, showed that 46% of patients left hospital to live with other family members, usually parents or spouses. Analysis of destination suggested that the extent of patient-family connectedness increases when the patient is younger, has had fewer admissions, or has had the illness for a shorter period of time.

Activities of Daily Living↗

Retinoids modify regulation of endogenous gene expression by vitamin D3 and thyroid hormone in three osteosarcoma cell lines.

1 alpha,25-Dihydroxyvitamin D3 (D3), T3, and retinoids are necessary for normal skeletal development, and their actions are interdependent due to the heterodimerization capabilities of their receptors. We investigated the hypothesis that these hormones act on osteoblasts directly to produce complex target gene responses resulting from multiple hormone interactions. Physiological interactions among D3, T3, and retinoid signaling were analyzed in serum-free cultures of the osteosarcoma cell lines ROS 25/1, UMR106, and ROS 17/2.8. These cells express distinct stages of the osteoblast phenotype and coexpress appropriate hormone receptors. Regulation of collagen I alpha 1 and alpha 2, alkaline phosphatase, osteopontin, and osteocalcin messenger RNAs was dependent on the dose and duration of hormone stimulation and modified by cell confluence. Retinoids were required for comprehensive expression of phenotypic responses to D3 and T3 in each cell type and hormone interactions were both cell and target gene specific. Differing responses of target genes in each cell line may provide a molecular basis for discrete hormone actions seen at specific stages of osteoblast differentiation or skeletal development.

Animals↗

Characterization of thyroid hormone (T3) receptors in three osteosarcoma cell lines of distinct osteoblast phenotype: interactions among T3, vitamin D3, and retinoid signaling.

T3 is required for normal skeletal development, but its cellular targets in bone are unknown. T3 regulates target gene transcription via a specific nuclear receptor (T3R), which can heterodimerize with 9-cis-retinoic acid, 1 alpha, 25-dihydroxyvitamin D3, or retinoic acid receptors to modify T3 responsiveness. Serum-free cultures were developed to investigate hormone interactions in three osteosarcoma cell lines, ROS25/1, UMR106, and ROS17/2.8, that express fibroblast-like, preosteoblast, and mature osteoblast phenotypes. ROS25/1 expressed T3R alpha 1, but only low levels of T3R beta 1, whereas UMR106 and ROS17/2.8 cells expressed both receptor proteins. All cells expressed c-erb-A alpha 2 protein and equal levels of 1 alpha,25-dihydroxyvitamin D3 receptor, 9-cis-retinoic acid receptor, and retinoic acid receptor messenger RNAs. Endogenous T3R activity and the effects of D3 and 9-cis-RA on T3 responsiveness were determined in transfections using reporter genes containing T3 response elements from rat malic enzyme or alpha-myosin heavy chain genes. Cell-specific T3 responses were associated with differing patterns of T3R gene expression and stages of osteoblast phenotype expression. A change in T3R beta 1 gene expression during osteoblast phenotype differentiation may modify T3 action in developing bone.

Animals↗

Pharmacokinetics of pirmenol in young and elderly subjects.

The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.

Adult↗

Patent ductus arteriosus increases lung fluid filtration in preterm lambs.

Previous studies showed that increased pulmonary blood flow from a patent ductus arteriosus had little or no effect on the amount of fluid in the lungs of mechanically ventilated preterm lambs. The purpose of this study was to examine the effect of a patent ductus arteriosus on lung vascular permeability and to see whether increased pulmonary lymph flow might compensate for the increased rate of fluid filtration. Using a model that allows mechanical control of ductus patency, we studied the effects of increased pulmonary blood flow on lung vascular pressures in six mechanically ventilated premature lambs at 136 +/- 2 d gestation (mean +/- SD) (term = 145 d). We measured lung lymph flow and protein concentrations in lymph and plasma to assess pulmonary vascular fluid filtration and protein permeability. We studied each lamb during sequential steady state periods, first with the ductus open and then with it closed. When the ductus was open, pulmonary blood flow was twice what it was when the ductus was closed. Mean pulmonary artery pressure and left ventricular end-diastolic pressure were greater with the ductus open [40 +/- 5 torr (5.3 +/- 0.7 kPa) and 8 +/- 3 torr (1.1 +/- 0.4 kPa), respectively] than when it was closed [24 +/- 3 torr (3.2 +/- 0.4 kPa) and 4 +/- 2 torr (0.5 +/- 0.3 kPa), respectively]. When the ductus was open, lymph flow was 68% greater and lymph protein concentration was 17% lower than when the ductus was closed. Lymph protein clearance (lymph flow x lymph protein concentration/plasma protein concentration) was 39% greater when the ductus was open.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fasting urinary calcium/creatinine and hydroxyproline/creatinine values in young women with amenorrhoea and in matched eumenorrhoeic controls.

The present study was undertaken to compare fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (HP/Cr) values in young amenorrhoeic women with those of age and weight-matched menstruating women and to see whether restoration of menstruation would influence values. Thirty amenorrhoeic patients were matched with 30 controls. Higher Ca/Cr (0.393 (SD 0.213) vs 0.142 (0.89), p less than 0.001) and HP/Cr (0.025 (0.005) vs 0.020 (0.007), p less than 0.005) values were found in patients with hyperprolactinaemia or hypothalamic dysfunction associated with weight loss, anorexia nervosa or excessive exercise (n = 20), suggesting excessive bone loss in these amenorrhoeic patients, who are frequently oestrogen deficient. Furthermore when 9 amenorrhoeic patients with hypothalamic dysfunction became eumenorrhoeic their urinary Ca/Cr values fell (p less than 0.02). However, amenorrhoeic patients with polycystic ovaries (n = 10) had similar Ca/Cr and HP/Cr values as their controls. It is therefore probable that amenorrhoeic patients with polycystic ovaries are not at risk of osteopenia. The present findings suggest measurements of fasting urinary Ca/Cr and HP/Cr values are likely to prove useful in identifying patients with amenorrhoea who are rapidly losing bone, and in assessing their responses to therapy.

Adult↗

Understanding family variables in outcome research in schizophrenia.

Outcome studies in schizophrenia research consistently show the importance of family variables in predicting patient relapse. The concept of expressed emotion (EE) is clinically relevant, though concerns remain about its precise meaning. The history of the EE studies is reviewed in the light of other family research, and an alternative model of family emotional environment is proposed. A number of clinical implications are considered.

Adaptation, Psychological↗

Family violence and psychiatric disorder.

The relationship between family violence and psychiatric disorders was examined using standardized diagnostic interviews of 1200 randomly selected residents of a large Canadian city. The results showed that higher than expected proportions of those exhibiting violent behavior had a psychiatric diagnosis and the rate of violent behaviors in those with diagnoses (54.4%) significantly (p less than .0001) exceeds the rate in the remainder of the sample (15.5%). Particularly high rates of violence are found in those where alcoholism is combined with antisocial personality disorder and/or recurrent depression (80-93%). Also at high risk for violence are those who have made suicide attempts (over 50%) and those who have been arrested for non-traffic offences (two-thirds). These data suggest that psychiatric disorders have a strong relationship to violent behavior, and are not in agreement with the predominantly sociological explanations of family violence.

Adolescent↗

Continuous polarographic monitoring of intra-arterial oxygen in the perioperative period.

Intra-arterial PO2 (PiO2) was polarographically monitored in ten critically ill patients during induction of anesthesia, the intraoperative period, extubation, and the immediate postoperative period; 147 PiO2 values were then paired with simultaneous measurements of PaO2. Mean PiO2 closely followed mean PaO2 over a wide range of values (r = .97), and the continuous, online real-time PiO2 readings provided a useful early warning system for hypoxemia during crisis periods. Technical problems included catheter clotting from improper flushing, changes in PiO2 due to changes in body temperature, the need for in vitro and in vivo calibration, and sensor drift. However, these problems were resolved by appropriate catheter management and sensor calibration.

Blood Gas Analysis↗