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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 415 records · Page 23Linked to original sources
PubMed1996

Stress, coping and burnout in mental health nurses: findings from three research studies.

In this paper we present data from three research studies on stress, coping and burnout in mental health nurses. All three studies used a range of self report questionnaires. Measures included a demographic checklist, the General Health Questionnaire (GHQ-28), the Maslach Burnout Inventory, the DCL Stress Scale and the Cooper Coping Skills Scale. In all, 648 ward based mental health nurses were surveyed. There were no significant differences between levels of psychological distress on GHQ Total Score, but there were differences in caseness rates. In Study 3, some 38% of nurses were found to score at or above the criterion for caseness. The main stressors for ward staff were to do with staff shortages, health service changes, poor morale and not being notified of changes before they occurred. Differences in coping skills were found across studies. The study group with the highest stress scores also had the lowest coping skills scores. This was also associated with significantly higher alcohol consumption and greater self reported sickness absence. Scores on the Maslach Burnout Inventory showed higher levels of burnout amongst nurses in Study 3. These three studies have confirmed that stress is a problem for ward based mental health nurses. Two main implications arise from this work. Firstly we need models of the stress process that are empirically based, and which help us identify the moderating variables that reduce the impact of stressors on nurses. Secondly, we need to utilise this knowledge to deliver stress management interventions for staff. We end by outlining a model which may help us both understand the process of stress causation, and move towards our goal of stress reduction.

Adaptation, Psychological↗
PubMed1996

Aberrant 11beta-hydroxysteroid dehydrogenase-1 activity in the cpk mouse: implications for regulation by the Ke 6 gene.

Glucocorticoids have been used to create experimental polycystic kidney disease in rodents and to induce cysts in embryonic kidneys cultures. In addition, the plasma corticosterone levels are higher in a heritable murine model of polycystic kidney disease, cpk mice, in the first postnatal week. Previously, we had shown that the 11beta-hydroxysteroid dehydrogenase-1 (11betaHSD-1) gene is down-regulated in the cpk mice in a coordinated pattern with the Ke 6 gene. In this study, we measured the level of 11betaHSD-1 activity in kidney and liver tissues of cpk homozygote mice and found a reduction in its activity only in the kidney, not in the liver. The activity of the 11betaHSD-1 enzyme appears to be tightly correlated to the level of Ke 6 protein in these tissues. We discuss the possibility that the activity of the 11betaHSD-1 enzyme may be regulated by the Ke 6 enzyme. Ke 6 gene expression has been located to the outer stripe region of rodent kidneys, which is the same region of expression as that for the 11betaHSD-1 gene. These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11betaHSD-1 activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Mitochondria-rich, proton-secreting epithelial cells.

Several transporting epithelia in vertebrates and invertebrates contain cells that are specialized for proton or bicarbonate secretion. These characteristic 'mitochondria-rich' (MR) cells have several typical features, the most important of which is an extremely high expression of a vacuolar-type proton-pumping ATPase (H+V-ATPase) both on intracellular vesicles and on specific domains of their plasma membrane. Physiological modulation of proton secretion is achieved by recycling the H+V-ATPase between the plasma membrane and the cytoplasm in a novel type of nonclathrin-coated vesicle. In the kidney, these cells are involved in urinary acidification, while in the epididymis and vas deferens they acidify the luminal environment to allow normal sperm development. Osteoclasts are non-epithelial MR cells that use H+V-ATPase activity for bone remodeling. In some insects, similar cells in the midgut energize K+ secretion by means of a plasma membrane H+V-ATPase. This review emphasizes important structural and functional features of proton-secreting cells, describes the tissue distribution of these cells and discusses the known functions of these cells in their respective epithelia.

Animals↗
PubMed1996

Diagnosis of neonatal congenital heart defects by remote consultation using a low-cost telemedicine link.

To determine whether telemedicine could assist in the earlier diagnosis of neonates with congenital heart disease (CHD) in an area hospital remote from a paediatric cardiologist, we established a low-cost telemedicine link between the neonatal unit of a district general hospital and the regional paediatric cardiology unit. Realtime ultrasound images of babies suspected of having CHD were obtained by a paediatrician and transmitted for realtime interpretation by a paediatric cardiologist. In a four-month pilot study, 10 neonates were studied in this way. In eight of the ten cases, the diagnosis made over the telemedicine link was confirmed subsequently in a direct examination at the regional unit. In one case the patient died before the direct examination was possible. In one case two small muscular ventricular septal defects were missed on the remote examination. Our early experience suggests that, with realtime guidance by a paediatric cardiologist, transmitted images of sufficient quality to allow confirmation or exclusion of major cardiac defects can be obtained. This form of remote consultation should improve morbidity and mortality rates by reducing the waiting time for specialist diagnosis and treatment.

Cardiology Service, Hospital↗
PubMed1996

Testing and evaluation of a hip extensor tricycle for children with cerebral palsy.

The design and testing of a modified tricycle (hip extensor tricycle) designed to isolate and exercise the hip extensor muscles in children with cerebral palsy is presented. Initial laboratory tests involved stability evaluation and EMG studies of two normal children. Field evaluation involved five children diagnosed with cerebral palsy who were given hip extensor tricycles for home use during an 8-week test period. The hip extensor strength and gait pattern of the subjects were recorded at 2-week intervals. The clinical tests indicated that the hip extensor tricycle was more stable, and resulted in more hip extensor muscle activity, than the traditional therapeutic/exercise tricycle. A panel of experts judged that the gait patterns of four of the five subjects improved during the course of the study. Parent evaluations indicated that the use of the hip extensor tricycle improved the subjects' physical condition, coordination, sense of accomplishment, and self-esteem.

Bicycling↗
PubMed1996

Cytokine expression in multiple myeloma and monoclonal gammopathy: analysis by reverse transcription/polymerase chain reaction and quantitative PCR.

Cytokine messenger RNA expression was studied using the reverse transcription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGUS), 12 with post menopausal osteoporosis, (OP) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 and M-CSF were sought in view of their reported pathogenic role in myeloma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were found frequently in all four groups of patients. The only significant difference in cytokine expression between the groups was for IL-6 which was expressed in 17% of controls compared with 87% of patients with MM (p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients with osteoporosis (p < 0.02). Further analysis of IL-6 expression by quantitative PCR showed significantly higher IL-6 mRNA levels in MM compared with MGUS (p < 0.006). There was no correlation however between expression of individual cytokines and clinical features of myeloma such as osteolytic bone disease or hypercalcaemia. We conclude that expression of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also associated with a high prevalence of IL-6 expression when compared with controls it is probable that factors other than IL-6 are responsible for the local osteolytic lesions which characterise MM, but which are not seen in MGUS or osteoporosis.

Aged↗
PubMed1996

Induction of Heymann nephritis with a gp330/megalin fusion protein.

There is considerable evidence that glomerular deposits in Heymann nephritis, a rat model of membranous nephritis, result from shedding of immune complexes formed on podocytes and that the principal antigen is part of the extracellular domain of a cell surface glycoprotein receptor called gp330 or megalin. It has also been reported that the immunogen that induces Heymann nephritis is a complex formed between gp330 and the receptor-associated protein RAP. The recent elucidation of the primary structure of gp330 makes it possible to investigate the ability of defined portions of gp330, devoid of RAP, to induce Heymann nephritis. In the present study we show that a gp330-glutathione-S-transferase fusion protein, containing 137 amino acid residues (1114 to 1250) of the ectodomain, induces active Heymann nephritis and that heterologous antibodies against this fusion protein produce passive Heymann nephritis. By immunofluorescence, typical glomerular immunoglobulin deposits were found, but complement components were lacking and the rats did not develop proteinuria. In the active model, we obtained evidence indicating that the deposits contained portions of the ectodomain of gp330, including regions other than those of the fusion protein. Thus, the deposits were stained by polyclonal antibodies to gp330 and to the gp330 fusion protein, as well as by two monoclonal antibodies reactive with portions of the ectodomain of gp330, only one of which reacted with the fusion protein in vitro. Antibodies against the cytoplasmic domain of gp330 did not stain. Furthermore, we found that RAP was able to bind to gp330 in the glomerular deposits but not to the gp330 fusion protein in vitro. The results show that the region of gp330 spanning amino acid residues 1114 to 1250 contains peptides capable of inducing pathogenic antibodies of Heymann nephritis without a contributory role of RAP.

Amino Acids↗
PubMed1996

Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.

Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.

Adult↗
PubMed1996

Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1.

BACKGROUND: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. MATERIALS AND METHODS: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. RESULTS: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. CONCLUSIONS: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease.

Animals↗
PubMed1995

LLC-PK1 cell growth is repressed by WT1 inhibition of G-protein alpha i-2 protooncogene transcription.

The temporal expression of the early growth response gene (EGR-1) is one molecular mechanism for both maximal activation of the G alpha i-2 gene and accelerated growth in mitotically active predifferentiated LLC-PK1 renal cells. These events are dependent on an enhancer area in the 5'-flanking region of the G alpha i-2 gene that contains an EGR-1 motif (5'-CGCCCCCGC-3'). However, acquisition of the polarized phenotype in LLC-PK1 cells is accompanied by loss of EGR-1 expression and occupancy of the EGR-1 site by nuclear binding proteins other than EGR-1. We now demonstrate that one of these binding proteins is the Wilms' tumor suppressor (WT1). Furthermore, the temporal expression of WT1 in LLC-PK1 cells acquiring the polarized phenotype represses both G alpha i-2 gene activation and growth in these cells. These findings suggest the existence of differentiation-induced pathways in LLC-PK1 cells that alternatively abrogates EGR-1 and promotes WT1 gene expression, thereby modulating a target protooncogene G alpha i-2 that is participatory for growth and differentiation in renal cells. These studies emphasize the usefulness of the LLC-PK1 renal cell as a model to elucidate normal programs of genetic differentiation in which WT1 participates.

Animals↗
PubMed1995

Alimentary lymphoma in cats: 28 cases (1988-1993).

OBJECTIVE: To evaluate response to chemotherapy in cats with alimentary lymphoma and to determine factors associated with survival time. DESIGN: Retrospective case series. ANIMALS: 28 cats with alimentary lymphoma that underwent chemotherapy. RESULTS: In all cats, the diagnosis had been established by means of cytologic or histologic examination of ultrasound-guided aspirates and biopsy specimens (18 cats), histologic examination of surgically obtained biopsy specimens (7 cats), or examination of specimens obtained endoscopically (3 cats). Clinical signs included anorexia, weight loss, vomiting, and diarrhea. Twenty-seven cats were treated with vincristine sulfate, cyclophosphamide, and prednisone; 1 was treated with chlorambucil and prednisone. Survival time ranged from 2 to 2,120 days (median, 50 days). Nine cats achieved complete remission (remission time ranged from 30 to 1,700 days; median, 213 days), 2 achieved partial remission, and 17 failed to respond to chemotherapy. Sex, FeLV status, hematocrit, serum total protein concentration, site and extent of gastrointestinal involvement, and clinical stage were not found to be associated with survival time. CLINICAL IMPLICATIONS: Cats with alimentary lymphoma are poorly responsive to treatment with vincristine, cyclophosphamide, and prednisone; however, a small subset of cats may have long survival times.

Animals↗
PubMed1995

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.

Adenocarcinoma↗
PubMed1995

Template recognition by an RNA-dependent RNA polymerase: identification and characterization of two RNA binding sites on Q beta replicase.

Two different SELEX protocols were used to generate two classes of RNA ligands that bound Q beta replicase with nanomolar equilibrium dissociation constants. One set of RNAs appeared to exist as pseudoknots with conserved loop sequences. These ligands bound Q beta replicase and ribosomal protein S1 with equal affinities, indicating that the RNAs bind the replicase through its S1 subunit. The second class of ligands bound the replicase via a pyrimidine rich region. The two sets of ligands did not compete for binding to Q beta replicase, demonstrating that the two RNA families bind unique sites on the phage polymerase. Because the second class of ligands bound ribosomal protein S1 very poorly, it is likely that the second RNA binding site is located on one of the three remaining replicase subunits. Published sequences of RNAs replicated by Q beta replicase possess similarities to the two classes of RNA ligands, providing a possible solution to the question of template recognition by the phage polymerase.

Base Composition↗