Compression ultrasonography for diagnosing deep vein thrombosis. Colour Doppler provides useful information.
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Humans↗
Biomedical subjects
S Richards
Publications and source records attributed to S Richards.
IMPROVE: bridge over troubled waters.
BACKGROUND: The original collaborative project was described in a 1995 Journal article titled "Competing HMOs Collaborate to Improve Preventive Services." IMPROVE (IMproving PRevention through Organization, Vision, and Empowerment) was a large randomized controlled trial using continuous quality improvement to implement clinical systems to improve the delivery of adult preventive services in primary care settings. The project was funded by the Agency for Health Care Policy and Research and initiated as a collaboration between two health maintenance organizations (HMOs) in the Twin Cities: Health Partners and Blue Plus. METHODOLOGY: Forty-four clinics were recruited for the study. Initially the 22 intervention clinics received the multifaceted intervention of leadership support, training on CQI and prevention systems, and consultation and networking opportunities. Next, the comparison clinics received similar assistance, and other clinics were invited into the collaboration. Ultimately, 57 clinics were involved in the project. Multiple collaborations--among clinics, leaders, and HMOs--developed during the project. STATUS: Despite turmoil in the environment during the project, many benefits have been described, including enhanced leadership, growth of systems thinking, better change management skills, and collaboration of competing organizations. SUMMARY: The IMPROVE collaboration survived and flourished in a very competitive market. It was viewed positively by clinicians, medical clinics, and HMOs, and its benefits have extended into the community.
Adult↗
Improved survival with early intensification: combined results from the Medical Research Council childhood ALL randomised trials, UKALL X and UKALL XI. Medical Research Council Working Party on Childhood Leukaemia.
The Medical Research Council (MRC) United Kingdom trial for childhood acute lymphoblastic leukaemia (UKALL X) randomised patients aged 0-14 years inclusive with an initial white blood count of less than 100 x 10(9)/l to receive an early intensification block, a late intensification block, both, or neither. The next trial, UKALL XI, for children aged 1-14 years, randomised between different central nervous system (CNS) directed therapies. At the beginning of the trial, all patients were also randomised between late intensification alone and both early plus late blocks. The effects of both the early and the late block in UKALL X alone have been reported previously. This paper examines the effect of the addition of the early intensification block to treatment which included late intensification, combining the data from UKALL X and the first part of UKALL XI. Early intensification was associated with fewer bone marrow relapses and a reduction in the odds of death of 0.63 (95% confidence interval: 0.46-0.87). Survival was significantly improved with an increase at 5 years of 8%, from 79 to 87%. Following this demonstration that early intensification improves survival, the effect of a third intensification block is under investigation.
Adolescent↗
Comparison of bone marrow transplant and chemotherapy for relapsed childhood acute lymphoblastic leukaemia: the MRC UKALL X experience. Medical Research Council Working Party on Childhood Leukaemia.
We examined the outcome of the 489 children with acute lymphoblastic leukaemia (ALL) who relapsed in the UKALL X trial, and produced graphical displays of adjusted comparisons of event-free survival (EFS) for chemotherapy versus bone marrow transplantation (BMT) from a sibling or volunteer unrelated donor, and autologous BMT (ABMT). EFS at 5 years was only 3% (95% CI 0-6%) for children who relapsed in the bone marrow (BM) within 2 years of diagnosis, irrespective of type of post-relapse treatment, whereas for those with late extramedullary relapse it was 66% (95% CI 48-85%). Comparison of the types of treatment did not show benefit for ABMT. For allogeneic BMT the overall reduction in the odds of an event was 26% (95% CI 1-51%) (2P= 0.05), resulting in an absolute increase in 5-year event-free survival of 14% (from 26.4% to 40.7%). New approaches are needed for children with early BM relapses whose prognosis is virtually hopeless with current therapy; however, a conventional chemotherapy approach may be justifiable for late extramedullary relapses. For the remaining patients (71%), with later BM or early extramedullary relapses, the optimal treatment is still not clear. This uncertainty warrants a formal randomized comparison of BMT and chemotherapy, to avoid the biases due to unmeasurable selection factors.
Adolescent↗
The relationship of coping style to dysphoria, anxiety, and anger.
This study examines Problem-focused Coping and Emotion-focused Coping, as measured by the Revised Ways of Coping Checklist, in relation to Dysphoria, Anxiety, Anger, Social Support, and course grades in psychology. Women university students (N = 245) were assessed two times six weeks apart. Problem-focused Coping was significantly negatively correlated with scores on the Center for Epidemiological Studies-Depression scale and with scores on the Self-rating Anxiety Scale at both time periods. Emotion-focused Coping was significantly positively correlated with scores on these scales and with scores on the State-Trait Anger scale at both times. Emotion-focused Coping was significantly negatively correlated with scores on the Social Support Questionnaire at both times and significantly negatively correlated with grades.
Adaptation, Psychological↗
Both paroxysmal nocturnal hemoglobinuria (PNH) type II cells and PNH type III cells can arise from different point mutations involving the same codon of the PIG-A gene.
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Adult↗
Detection and biochemical characteristics of the receptor for complexes of soluble CD14 and bacterial lipopolysaccharide.
Soluble CD14 (sCD14) has been found to bind LPS and mediate LPS activation of several cell types. It has been postulated that sCD14-LPS complexes induce cell responses by interacting with a cell surface structure, which, in turn, triggers cell activation. There has been no biochemical evidence, however, for a direct interaction of sCD14 with a cell surface structure, and the putative receptor has not been identified. To rigorously test this hypothesis, we studied the interaction of human rsCD14 with cells in the absence of serum and in the presence and the absence of LPS. We found 1) there was specific and saturable binding of 125I-sCD14, indicative of a typical receptor-ligand interaction, to several cell types, including endothelial cells, epithelial cells, astrocytes, and human monocytes; 2) specific binding to all the cell types and IL-6 induction in membrane-bound CD14 (mCD14)-negative cells occurred only when both sCD14 and LPS were present; 3) competitive displacement experiments of 125I-sCD14 binding to astrocytes and Scatchard plots revealed a binding of high affinity (Kd = 3.3 +/- 0.4 nM) and approximately 25,000 single class binding sites/cell; 4) the steady state for the association of 125I-sCD14 was obtained after 180-200 min; 5) chemical cross-linking experiments revealed the association of sCD14 with a binding structure of approximately 216 kDa; 6) binding of 125I-sCD14 to CD14-expressing cell transfectants was about 50% lower than that to nontransfected cells. Maximal binding, however, was recovered after removing mCD14, suggesting that the sCD14-LPS receptor may also interact with mCD14. These results provide direct biochemical evidence for the existence of a cell surface signal-mediating binding structure for LPS-bearing sCD14 and suggest that this structure may represent the signaling unit of the postulated multimeric LPS receptor in mCD14-bearing cells.
Animals↗
A phase 1 study to address the safety and efficacy of granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in active rheumatoid arthritis.
OBJECTIVE: To examine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) alone for the mobilization of peripheral blood progenitor cells in patients with resistant active rheumatoid arthritis (RA). METHODS: Five patients with resistant active RA were studied. A dose of 5 microg/kg of G-CSF (Filgrastim) was given subcutaneously each day for 5 days, and the number of stem cells mobilized into the peripheral blood was assessed by daily CD34 counts. RA disease activity was assessed by standard clinical methods. RESULTS: The absolute numbers of peripheral blood CD34+ cells peaked on day 4, with a mean value of 0.025 x 10(9)/liter (range 0.013-0.048 x 10(9)/liter). There was no significant change in disease activity during the study or in the month following therapy. CONCLUSION: Using G-CSF alone, CD34+ progenitor peripheral blood cells were mobilized in numbers suitable for leukopheresis. G-CSF therapy was well-tolerated in patients with active RA, and was not associated with a flare during treatment or in the month following treatment.
Adult↗
Integrative erectile biology: the role of signal transduction and cell-to-cell communication in coordinating corporal smooth muscle tone and penile erection.
The contractility of corporal smooth muscle plays a critical role in the entire erectile process in man. Moreover, in the absence of severe vascular disease, or congenital or other structural abnormalities/malformations, relaxation of the corporal smooth muscle is both necessary and sufficient to elicit a sustained erection. As such, understanding the initiation, maintenance and modulation of corporal smooth muscle tone is an absolute prerequisite to the improved understanding, diagnosis and treatment of erectile dysfunction. Despite this fact, identification of both the precise mechanistic basis by which endogenous and exogenous vasomodulators exert their effects on individual corporal smooth muscle cells, and moreover, the process by which these signals are spread among the diverse array of parenchymal cells in the paired corpora, remains somewhat of a physiological enigma. Therefore, the goal of this report is two-fold: first, to review current knowledge of the regulation of corporal smooth muscle tone at the cellular and molecular level; and second, to outline a cogent explanation for the rapid and syncytial integration of the effects of diverse stimuli among corporal smooth muscle cells in the human penis.
Animals↗
Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukaemia Working Party.
Cytogenetic classification of 350 adults with acute lymphoblastic leukaemia on MRC UKALL XA trial showed the following statistically significant associations: t(9;22) (11%) increased with increasing age and leucocyte counts (WBC) and most had a C/pre-B immunophenotype. t(4;11) (3%) was associated with higher WBCs, increasing age and null immunophenotype. Other abnormalities of 11q (abn11q) (4%) were associated with male sex and T-cell ALL. High hyperdiploidy (7%) and abn9p (5%) decreased with increasing WBC. High hyperdiploid patients were younger and tended to have C/pre-B ALL. Triploidy/tetraploidy (3%) decreased and pseudodiploidy (11%) increased with increasing WBC. Cytogenetic classification was prognostically important (chi-square for heterogeneity of classification = 53.56; P < 0.0001) and added significance to age, sex and WBC. A poor prognosis for patients classed as t(9;22) (13% disease-free survival at 3 years), as t(4;11) 24% at 3 years) and hypodiploid (11% at 3 years), and good prognosis for abn12p (4% of subjects) and high hyperdiploidy (74% and 59% at 3 years respectively) were statistically significant, but the 54% 3-year disease-free survival for patients with t(1;19) was not. The prognosis of patients classed as t(9;22) was independent of other single variables. Abn12p, abnormalities of 11q (including t(4;11) cases) and hypodiploidy added prognostic significance to all other variables combined.
Adolescent↗
Immunological abnormalities of chronic large granular lymphocytosis.
Chronic large granular lymphocytosis is a relatively common condition and comprises a clinically heterogenous group of patients. Phenotypically these can be divided into CD3+ (T cell) and CD3-(NK cell) expansions. They are characterized by a benign clinical course and a mild lymphocytosis, though a specific subgroup have a history of auto-immune disease and cytopenias. In order to develop a better understanding of the immunological abnormalities associated with this condition we examined systematically serum samples from 92 such patients for the presence of auto-antibodies, acute phase proteins and immunoglobulin levels. Auto-antibodies were found in 34% of patients and rheumatoid factor in 26%, though only half of these had active arthritis. Anti-neutrophil antibodies were negative in all cases. Quantitative immunoglobulin abnormalities were frequent with a distinct paraprotein present in three patients. The high incidence of multiple immunological abnormalities in these patients ranged from polyclonal hypergammaglobulinaemia and auto-antibodies through to monoclonal gammopathy. The aetiology of these abnormalities was unclear and undoubtedly complex, and should necessarily form part of the diagnostic investigations for all patients with persistent large granular lymphocyte expansions.
Antibodies, Antinuclear↗
Association of the TNFa2 microsatellite allele with the presence of colorectal cancer.
Independently, our two groups collaborating in this report performed association studies to consider the influence of the TNF region within the human MHC on the presence of colorectal cancer. In the Glasgow Study, 84 colorectal cancer patients were compared with 91 controls at the TNFa microsatellite locus. Analysis of individual alleles by Fisher's exact test revealed a significant overrepresentation of the TNFa2 allele in the colorectal cancer group, after correcting for multiple comparisons. In the Essen Study, 47 colorectal cancer patients were compared with 117 matched controls, and the hypothesis of TNFa2 overrepresentation in colorectal cancer was confirmed. These data provide evidence for the involvement of the TNF locus in the pathogenetic etiology of colorectal cancer.
Alleles↗
Antidepressant use over time in a rural older adult population: the MoVIES Project.
OBJECTIVE: To examine the use of antidepressant drugs over time among community-based older persons. DESIGN: A longitudinal community study with four approximately biennial data collection waves (1987-1996). SETTING: A low-socioeconomic status rural older community-based population in Southwestern Pennsylvania. PARTICIPANTS: A total of 1681 individuals with a mean age of 72.9 years at study entry, MEASUREMENTS: Antidepressant drug use, demographics, and health services utilization by self-report. RESULTS: Antidepressant use was reported by less than 5% of the population during all four waves. It was associated with female gender, use of mental health services, presence of five or more depressive symptoms, and use of five or more prescription drugs, but not with age. During the four waves, tricyclics accounted for 84.6%, 85.3%, 78.4%, and 45.5% of total antidepressants used, whereas selective serotonin reuptake inhibitors (SSRIs) accounted for 2.6%, 11.8%, 8.1%, and 36.4%. CONCLUSIONS: Overall, our data on antidepressant use in this rural older population mirror national trends away from tricyclics and towards SSRIs. Our findings also suggest underutilization of mental health services and antidepressant drugs in this population.
Aged↗
Clinical-neurologic, cytogenetic and molecular aspects of the Prader-Willi and Angelman syndromes.
The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are human neurogenetic disorders involving the imprinting mechanism, at the 15q11-13 chromosome region. The predominant genetic defects in PW are 15q11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy. In contrast, maternal deletions and paternal chromosome 15 uniparental disomy are associated with a different neurogenetic disorder, the AS. In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q11-13 loci. We studied 5 patients suspect of PWS and 4 patients suspect of AS who were referred to the Medical Genetics Unit at the University Hospital of Medical School from Ribeirão Preto. Our objective was to establish the correct clinical and etiological diagnosis in these cases. We used conventional cytogenetics, methylation analysis with the probe KB17 (CpG island of the SNRPN gene) by Southern blotting after digestion with the Xba I and Not I restriction enzymes. We studied in patients and their parents the segregation of the (CA)*** repeats polymorphisms by PCR, using the primers 196 and IR4-3R. All the patients had normal conventional cytogenetical analysis. We confirmed 3 cases of PWS: one by de novo deletion, one by maternal chromosome 15 uniparental disomy and one case with no defined cause determined by the used primers. We confirmed 2 cases of AS, caused by de novo deletion at the 15q11-13 region, and one case with normal molecular analysis but with strong clinical characteristics.
Adolescent↗
Variability of anticardiolipin antibody isotype distribution in 3 geographic populations of patients with systemic lupus erythematosus.
OBJECTIVE: To investigate the prevalence of anticardiolipin antibodies (aCL) and isotype distribution and their clinical associations with the features of the antiphospholipid syndrome (APS) in 3 different ethnic groups of patients with systemic lupus erythematosus (SLE). METHODS: The study population consisted of 152 African-American, 136 Afro-Caribbean (Jamaican), and 163 Hispanic (Colombian) unselected patients with SLE. Serum samples were studied for the prevalence of aCL and isotype distribution. All aCL measurements were performed in the same laboratory by ELISA. RESULTS: Positive results for 1 of the 3 aCL isotypes were found in 42 African-Americans (28%), 28 Afro-Caribbeans (21%), and 43 Hispanics (26%). IgG aCL was the dominant isotype in Hispanic and African-American patients, while IgA was the dominant isotype in Afro-Caribbeans. Of note, IgA aCL was found in all Afro-Caribbean patients who were aCL positive, while only 3 patients in this group had IgG aCL and 2 had IgM aCL. Clinical features of the APS were found to correlate better in Hispanics than in African-Americans and Afro-Caribbean patients with aCL isotypes. CONCLUSION: Our data suggest the existence of ethnic differences in the prevalence and isotype distribution of aCL as well as in their clinical relevance in patients with SLE. Further studies of the role of genetic and/or environmental factors in the observed differences are required.
Adolescent↗
Which analgesia? Guidelines to pharmacological pain control.
The aim of this guide is to provide an accessible resource for nursing and medical staff on current pharmacological methods of pain control-the different types of analgesics that are available, the indications for each and their doses, formulations, contraindications and side-effects. The focus is on the drugs used in the management of postoperative pain, although their uses obviously extend to the management of other types of pain, such as chronic pain, cancer pain or pain relief during palliative care. Patient-controlled analgesia and the management of pain in children are not included in this guide.
Adult↗
The distribution of Met-enkephalin like immunoreactivity in the brain of Apteronotus leptorhynchus, with emphasis on the electrosensory system.
The distribution of Met-enkephalin-like immunoreactivity in the brain of the electric fish, Apteronotus leptorhynchus was analysed by immunohistochemistry. The majority of Met-enkephalin immunoreactive neurons were found in the hypothalamus. Dense Met-enkephalin immunoreactive fiber plexuses were seen in the hypothalamus and ventral forebrain. In the dorsal telencephalon an olfacto-recipient region (ventral subdivision of the dorsolateral forebrain) was specifically and densely innervated. Regions of the brain known to be involved in electrocommunication also received a substantial innervation by Met-enkephalin-like immunoreactive fibers. This distribution of immunoreactive fibers in the brain of this gymnotiform fish indicates that Met-enkephalin may be generally involved in the regulation of sensory, neuroendocrine and reproductive functions and specifically in the regulation of electrocommunication.
Animals↗
Mutations in the Drosophila pushover gene confer increased neuronal excitability and spontaneous synaptic vesicle fusion.
We describe the identification of a gene called pushover (push), which affects both behavior and synaptic transmission at the neuromuscular junction. Adults carrying either of two mutations in push exhibit sluggishness, uncoordination, a defective escape response, and male sterility. Larvae defective in push exhibit increased release of transmitter at the neuromuscular junction. In particular, the frequency of spontaneous transmitter release and the amount of transmitter release evoked by nerve stimulation are each increased two- to threefold in push mutants at the lowest external [Ca2+] tested (0.15 mM). Furthermore, these mutants are more sensitive than wild type to application of the potassium channel-blocking drug quinidine: following quinidine application, push mutants, but not wild-type, display repetitive firing of the motor axon, leading to repetitive muscle postsynaptic potentials. The push gene thus might affect both neuronal excitability and the transmitter release process. Complementation tests and recombinational mapping suggest that the push mutations are allelic to a previously identified P-element-induced mutation, which also causes behavioral abnormalities and male sterility.
Animals↗