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Biomedical subjects

D Clarke

Publications and source records attributed to D Clarke.

At least 163 records · Page 9Linked to original sources

The Northfield experiments.

The Northfield Experiments took place at Hollymoor Hospital, Northfield, Birmingham, during World War II. The first experiment was conducted by Bion & Rickman. The second evolved gradually; many people contributed to its success, including Foulkes, Main and Bridger. The experiments were an important landmark in the evolution of theory and practice in group psychotherapy and in the therapeutic community movement. They were not carried out solely as responses to the need for mass treatment of neurotic disorders among army personnel; antecedent factors, the theoretical orientation of the practitioners and the nature of army life were equally important. The two experiments differed in pace and in recognition of the needs of higher-order systems, particularly the military hierarchy. They shared many underlying concepts, including responsibility to society, the therapeutic use of groups (including the hospital community) and an emphasis on process. Lessons learned at Northfield remain relevant to the practice of psychiatry today.

Combat Disorders↗

Pulmonary manifestations of the eosinophilia-myalgia syndrome associated with tryptophan ingestion.

Pulmonary manifestations are not infrequent in the L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). However, previous reports have not described the results of longitudinal pulmonary function, exercise testing, high-resolution computerized tomographic (HRCT) scanning of the chest, or detailed bronchoalveolar lavage (BAL) analysis. We report six patients with EMS who had dyspnea. The diffusing capacity for carbon monoxide was decreased in five patients tested. Exercise testing with arterial blood gas sampling in three patients was consistent with pulmonary vascular or parenchymal disease. Serial exercise testing in two of these patients demonstrated marked improvement temporally associated with corticosteroid treatment. In four patients, HRCT scanning of the chest was abnormal. One of these patients showed no abnormality on routine chest roentgenogram. Two patients undergoing BAL exhibited increased eosinophils in the lavage fluid; a third had elevated lymphocytes. Serial measurements of fibroblast proliferation-stimulating-activity in samples of BAL fluid obtained from serial examinations in two patients exhibited heightened pretreatment activity that returned to the normal range following corticosteroid therapy. In these two patients, increased proportions of T-suppressor/cytolytic (CD8+) cells were observed in the BAL fluid. Despite aggressive immunosuppressive therapy, one of the patients died of respiratory failure. Another remains markedly dyspneic with pulmonary hypertension. Of the remaining four patients, two exhibited resolution of pulmonary symptoms after systemic corticosteroid therapy, and two experienced partial improvement.

Adult↗

Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.

A new human liver UDP-glucuronosyltransferase (HlugP4) has been cloned and expressed in cell culture. The expressed enzyme has a molecular mass of 56 kDa and preferentially catalysed the glucuronidation of halogenated and bulky alkyl phenols. The C-terminal half of the sequence (246 amino acids) is 96% identical with the same portion of HlugP1, whereas the N-terminal half of the deduced protein sequences are only 38% identical. These results suggest that the two isoenzymes may be derived from the same gene by differential splicing of the gene product.

Amino Acid Sequence↗

Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome.

Liver biopsy samples were obtained from eight Crigler-Najjar patients. Bilirubin UDPGT activity, assayed by a microassay with HPLC analysis, was not detectable in type I livers, and low levels (9-26% of controls) of monoglucuronide conjugates only were observed in type II livers. 1-Naphthol UDPGT activity was normal in most patients, where membrane integrity was maintained by correct sample procurement and preparation. Our data on type II livers suggest that a defect in UDPGA transport is an unlikely cause of the hyperbilirubinaemia, but reduced affinity for UDPGA was observed in one sample. Analysis of four patient liver samples by immunoblot analysis revealed the heterogeneous nature of this inherited disease within the patient population, and one sample where 1-naphthol UDPGT activity was considerably reduced appeared to correlate with the non-detection of a phenol UDPGT protein. Progress towards a molecular genetic diagnosis of Crigler-Najjar syndromes is discussed.

Aged↗

Hemolysis due to branch pulmonary stenosis after the arterial switch procedure.

An infant with d-transposition of the great arteries underwent arterial switch operation using the modified Jatene technique. Severe bilateral branch pulmonary artery stenosis and mechanical hemolysis subsequently developed. The hemolysis resolved after surgical repair of the stenotic arteries. Probable causes are discussed.

Anemia, Hemolytic↗

Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!

Surgical haemoclips have been left in situ in 27 consecutive patients conservatively operated on for early breast cancer by two surgeons in Newcastle, New South Wales, to demarcate the limits of the excision cavity for accurate postoperative irradiation. As anticipated, the position of these clips varied widely in relation to the patient's recollection of the position of the original lump, the surgical notes, and the surgical scar. In addition the dimensions of the clipped area also varied considerably. So great was the variation in position of the clips that incomplete coverage of the excision cavity in the 'coronal' (en face) plane using an electron field could have occurred in an estimated 10/24 (42%) evaluable cases had surgical clips not been left in situ. Depth of the surgical clips below the skin surface also varied markedly between patients. In 19/26 (73%) evaluable cases the clips were observed to be sited 3 cm or more below the skin surface, while in only 5/26 (19.2%) were the clips found to be 2 cm or less deep to the surface. Had a 9 MeV beam from our Clinac 1800 been used to treat all the cases, a major underdose of the excision cavity would have been likely in 21/26 (81%) evaluable cases. This figure would be improved to 11/26 (42%) had a 12 MeV beam been used--still a very high figure. Neither of these points have received much attention in the literature. This small study sounds a distinct warning and needs to be repeated on a larger scale.

Breast Neoplasms↗

Small bowel haemorrhage due to cytomegalovirus vasculitis.

A case is described of a life threatening vasculitis of the small bowel leading to massive gastrointestinal haemorrhage which was apparently due to cytomegalovirus inclusion disease. Reactivation of cytomegalovirus probably followed the treatment of Wegener's granulomatosis with corticosteroids and azathioprine. This patient was treated successfully by surgical excision of the affected segment of ileum together with intravenous ganciclovir.

Aged↗

DNA flow cytometry of follicular non-Hodgkin's lymphoma.

S-phase fraction, an index of cellular proliferation, and DNA ploidy were measured by DNA flow cytometry in a retrospective study of lymph node biopsy specimens from 83 cases (before treatment) of follicular non-Hodgkin's lymphoma, Working Formulation categories B and C. The correlations between these measures and survival, clinical stage, symptoms and histopathological factors were investigated. Aneuploidy was rare (n = 16) and had no effect on length of survival or transformation to high grade lymphoma. The overall mean S-phase fraction was 3.6%; for the whole series increasing S-phase fraction was associated with decreased survival. A high S-phase fraction (more than 5%) in initial biopsy specimens was also associated with an increased risk of subsequent high grade transformation at relapse. There was no difference between the survival or proliferative activity of tumours composed of mainly small cleaved cells compared with those composed of mixed small and large cells. There was no difference in survival or proliferative activity between tumours showing a pure follicular growth pattern and those with a mixed follicular and diffuse growth pattern. Multifactorial analysis showed that an S-phase fraction of more than 5% and B symptoms were the most important factors determining survival in these follicular non-Hodgkin's lymphomas.

Adult↗

Alpha-1 adrenergic receptors in renal medullary collecting duct cells.

The stimulation of alpha-1 adrenergic receptors in the mammalian nephron increases sodium reabsorption. In this study, alpha-1 adrenergic receptors in the inner medullary collecting duct (IMCD) cells were examined by radioligand binding technique. The IMCD cells were prepared from the rabbit kidney by incubating the inner medullary slices with collagenase and treating the isolated cells with hypotonic solution to lyse cells other than IMCD cells. The equilibrium binding of [3H]prazosin to IMCD cell homogenate was measured after incubation for 30 min at 25 degrees C in the absence (total binding) and the presence (nonspecific binding) of 100 microM phentolamine. The specific binding (the difference between total and nonspecific binding) of [3H]prazosin was saturable with a Bmax of 30 fmol/mg of protein and Kd of 0.9 nM. The displacement of [3H]prazosin binding to IMCD cells by adrenergic antagonists and agonists displayed the order of potency: beta-4-hydroxyphenyl-ethyl-amino-tetralone greater than phentolamine greater than naphazoline greater than epinephrine greater than yohimbine greater than norepinephrine greater than phenylephrine greater than propranolol. Because IMCD cells in the kidney have a hypertonic environment, the specific binding of [3H] prazosin to IMCD cells was also measured in a buffer that was made hypertonic (1200 mOsmol/kg of water) with NaCl and urea, the major solutes of the renal medulla. The hyperosmolality increased the Kd of [3H]prazosin to 5.2 mM without a change in its Bmax.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia.

The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML is reflected by their reduced capacity to bind to marrow derived stromal layers in vitro. Whereas normal bone marrow Bl-CFC bind irreversibly to cultured stromal layers (and none are found in normal blood), the Bl-CFC in CML bind transiently and then detach. The normal cell adhesion mechanism is partially sensitive to treatment with phosphatidylinositol-specific phospholipase C (Pl-PLC), indicating the participation of a phosphatidylinositol (Pl)-linked structure; however, when CML cells were treated with Pl-PLC it had no effect on progenitor binding. Two other Pl-linked structures, decay-accelerating factor (DAF) and lymphocyte function associated antigen-3 (LFA-3) were normally expressed on CD34 positive CML cells and normally susceptible to Pl-PLC treatment. The treatment of normal cells with Pl-PLC, to mimic the situation in CML, resulted in the indiscriminate and inefficient binding of Bl-CFC to stroma. Moreover, treatment of the normal cells with 5637 conditioned medium (CM), which contains haemopoietic growth factors, also reduced the binding capacity of normal Bl-CFC; 5637CM treatment did not alter the expression of DAF. It is proposed that a Pl-linked cell adhesion molecule (CAM) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst, in normal cells, CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors.

Antigens, CD↗

Creating a climate for the development of nursing.

In this paper, the authors describe the creation of a climate for change and development in the clinical setting. They discuss the emergence of roles of clinical nurse specialist-manager as key practitioner roles in developing the milieu for clinical practice development. The need to build links with education and develop clinical education roles are also explored. In creating a Nursing Development Unit, the authors argue that it is possible to create a setting where innovation can take place, nursing care can be improved, and theory can be put into practice.

Clinical Nursing Research↗

Haemopoietic stem cell subpopulations in mouse and man: discrimination by differential adherence and marrow repopulating ability.

Based on the properties of differential cell adherence, we have devised two assays for early progenitor cells in human bone marrow. One progenitor cell population binds to plastic and to pre-formed bone marrow derived stromal layers (P+S+) and gives rise to non-adherent granulocyte-macrophage colony-forming cells (GM-CFC); the other binds to stromal layers but not to plastic (P-S+); both are separable from GM-CFC which are P-S-. We have evaluated the relevance of differential binding properties to marrow repopulation in a murine model. Murine stem cells (spleen colony-forming cells--CFU-S) can be separated into P+S+, P-S+ and P-S- subpopulations by differential adhesion, thus paralleling the progenitor cell subpopulations in human marrow. Post irradiation (850 cGy X-rays) studies have shown that the P+S+ cells are essential for survival and recovery of marrow, spleen and blood cell populations. Also, in a model for purging autografts, we have demonstrated that the leukaemic cells can be separated from P+S+ repopulating cells by exploiting their different binding properties.

Animals↗

Hemopoietic progenitor cell binding to the stromal microenvironment in vitro.

Primitive clonogenic progenitor cells in human bone marrow bind to preformed marrow-derived stromal layers in vitro and generate colonies of blast cells. The binding interaction does not require calcium or magnesium ions and occurs equally well in serum-free and serum-supplemented culture medium. It does not appear to involve known cell adhesion molecules (CAMs) for which monoclonal antibodies are available (integrins, N-CAM, LFA-1, and ICAM-1), and we were unable to demonstrate a role for the progenitor cell antigen CD34 in progenitor cell adhesion to cultured stroma. The CAM expressed by the blast colony-forming cells may exist in transmembrane or phosphatidylinositol (PI)-linked forms because it is only partially degraded by exposure to trypsin or to PI-specific phospholipase C. However, binding of these cells to stroma is not prevented in the presence of monoclonal antibodies reacting with known PI-linked structures (Thy-1, CD14, and CD16). It is either masked by neuraminidase-sensitive residues or is no longer expressed as cells mature, respectively, along the granulocytic or erythroid lineages. The properties of the hemopoietic progenitor CAM are discussed with reference to the properties of other CAMs and of hemopoietic progenitor cell markers.

Antibodies, Monoclonal↗

Peritoneal dialysis following open heart surgery in children.

Over the course of the last 5 years, we have instituted peritoneal dialysis on 26 (7.7%) of 338 complex postoperative cardiac bypass cases. The mean age of dialysis patients was 0.64 +/- 0.75 years with a range of 0.1-2.5 years. The indications for the start of dialysis were oliguria (15 cases), fluid overload (three cases), hyperkalemia (one case), and anuria (seven cases). There were no complications as the result of dialysis, although two of the dialysis catheters had to be replaced. Dialysis successfully treated the starting indication in all cases. Dialysis was instituted at 47 +/- 50 (12-240) h after bypass, and lasted 111 +/- 134 (18-552) h; early institution of dialysis had no effect on mortality. Low cardiac output was a significant predictor of death in dialysis patients (p = 0.015). Age was a significant determinant of death (p = 0.0001) and the need for dialysis (p = 0.0043) in the total bypass population; the younger the patient, the greater was the likelihood of death or the need for dialysis. Age, however, was not a predictor of mortality in the peritoneal dialysis group.

Aging↗