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PubMed1991

Subjective dysfunction after stroke. A study with sickness impact profile.

In 1986, the functional capacity of 124 patients with an acute stroke was assessed one week after admission to Södertelje hospital, Sweden. In order to analyse health-related quality of life, interviews were undertaken to determine sickness impact 6-9 months after stroke. 57 of the 91 surviving patients could participate. 53 persons were living in their own homes. 70% had a clinically significant subjective dysfunction, which correlated both to the objective functional capacity and to age. Sickness Impact Profile was a useful measure, yielding information of value for planning of long-term rehabilitation and home care.

Activities of Daily Living↗
PubMedDate not supplied

Impairment and recovery profiles of sensory-motor function following stroke: single-case graphical analysis techniques.

Graphical analysis procedures have been developed to improve interpretation of sensory-motor tests from individual subjects following acute brain damage. The procedures have been applied to 11 unilateral stroke patients assessed serially over 12 months on a computerized quantitative sensory-motor test battery of which grip strength, arm speed, and tracking have been chosen for illustrative purposes. The results indicate that four graphs are necessary to fully demonstrate neurologic impairment and recovery of each sensory-motor function, although fewer graphs would be satisfactory in some applications. Such analyses have proven valuable in the display of serial performance of individual patients but demonstration of impairment and recovery is much more difficult than for group analyses.

Activities of Daily Living↗
PubMed1993

Experience with NORPLANT in Egypt.

Experience with the contraceptive NORPLANT in Egypt dates back to early 1980 when the first multicentre trial was initiated. To date, more than 3000 women have received this contraceptive at the Assiut University Family Clinic alone. Analysis of the overall experience in this clinic has indicated a 5-year cumulative continuation rate of 51 and a pregnancy rate of 1.8 per 100 women. Clinical pharmacology studies pertaining to the safety of NORPLANT in our community have indicated no deleterious effect on the lipid profile, liver functions and blood coagulation system. Two studies conducted in Egypt have indicated that the initiation of NORPLANT use shortly after delivery does not have any unfavourable effect on lactational performance, or on physical or psychomotor development of the breast-fed infants. This is particularly important in Arab and Moslem cultures where prolonged breast-feeding is emphasized. A study utilizing focus-group discussion to assess users' attitudes to NORPLANT has indicated the need to improve the informational/educational package given in the service by emphasizing certain cultural considerations. On the whole, this first implant method has proven to be safe and acceptable in Egypt, where there is a special need for long-term methods for contraception, particularly as sterilization is not socially acceptable.

Adult↗
PubMed1996

Frenchay Aphasia Screening Test: validity and comparability.

The Frenchay Aphasia Screening Test1 is a reliable test which can be used by non-specialists to discriminate between aphasia and normal language. Preliminary studies have shown good test-retest reliability, and the test itself is quick and simple to use. The present investigation examines the validity of the test by comparing the results of this test with those on more structured, detailed and frequently used assessments of aphasia -the Minnesota Test for Differential Diagnosis of Aphasia (MTDDA) and general performance in communication as reflected by the Functional Communication Profile. The results demonstrate a positive correlation between the tests, and this allows confidence in the use of this test by non-specialists as a screening instrument.

Aged↗
PubMed1992

Factors influencing accuracy of estimation of comprehension problems in patients following cerebrovascular accident, by doctors, nurses and relatives.

Previous work has shown that doctors, nurses and relatives are inaccurate at estimating the comprehension problem of stroke patients. Possible factors that influence the accuracy of these judgements were studied, including confidence of the respondents, the severity of the comprehension problems of the patients and factors specific to relatives (educational background and the length of the relative's relationship with the patient). Doctors, nurses and relatives involved with 30 recently aphasic stroke patients were asked to estimate how patients would perform on the comprehension sections of two tests (Western Aphasia Battery and Functional Communication Profile). Results show that although all respondents over-estimated patients' comprehension abilities, they were more accurate for patients who had mild problems. Doctors and nurses who were more confident about their predictions tended to be more accurate on some parts of the tests than those with less confidence, whereas relatives were equally inaccurate when giving high and low confidence judgements. Length of relationship and educational level did not predict relative's accuracy.

Aged↗
PubMed2006

Frameshift proteins in Alzheimer's disease and in other conformational disorders: time for the ubiquitin-proteasome system.

Neuronal homeostasis requires a constant balance between biosynthetic and catabolic processes. Eukaryotic cells primarily use two distinct mechanisms for degradation: the proteasome and autophagy of aggregates by the lysosomes. We focused on the ubiquitin-proteasome system (UPS) and discovered a frameshift protein for ubiquitin (UBB+1), that accumulates in the neuritic plaques and tangles in patients with Alzheimer's disease (AD). UBB+1, unable to tag proteins to be degraded, has been shown to be a substrate for ubiquitination and subsequent proteasomal degradation. If UBB+1 is accumulated, it inhibits the proteasome, which may result in neuronal death. We showed that UB+1 is also present in other tauopathies (e.g. Pick's disease) and in several polyglutamine diseases, but remarkably not in synucleinopathies (e.g. Parkinson's disease). Accumulation of UBB+1-being a reporter for proteasomal dysfunctioning- thus differentiates between these conformational diseases. The accumulation of UBB+1 causes a dysfunctional UPS in these multifactorial neurodegenerative diseases. Novel transgenic mouse models and large-scale expression profiling and functional analyses of enzymes of the UPS compounds - enabling us to identify the targets of the UPS in these conformational diseases - may now pave the way for intervention and treatment of AD.

Alzheimer Disease↗
PubMed1994

Profiles of chicken macrophage effector functions.

In contrast to the mammalian system, avian species lack the so-called "resident" or "harvestable" macrophage population in the abdominal exudate. However, macrophages can be recruited into the chicken's abdominal cavity (presumably from the blood monocyte pool) if an inflammatory agent such as Sephadex is injected. The kinetics of inflammatory cell recruitment in terms of time, cell type, and state of activation to perform a particular effector function is currently an active area of research. This report will provide information on several chicken macrophage effector functions, including in vivo chemotaxis, phagocytosis, bacterial uptake and killing, biosynthesis of nitric oxide and various enzymes, and monokines such as interleukin-1 and granulocyte colony-stimulating factor.

Acid Phosphatase↗
PubMed2026

Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation.

BACKGROUND: The pathogenesis of brucellar spondylitis (BLS) has traditionally been considered to be primarily limited to local osteoarticular lesions. With the proposal of the "gut-spine axis" concept, the role of intestinal microecological dysbiosis in inflammatory spinal diseases has attracted in an increase of attention. The overactivated inflammatory cytokine network not only mediates bone destruction and intervertebral disc damage, but also forms a bidirectional interaction with gut microbiota dysbiosis through the "gut-spine axis," collectively driving disease progression. However, the inflammatory mechanism by which gut microbiota participates in the pathological process of BLS remains largely unclear. METHODS: This study recruited 20 BLS patients and 20 healthy donors. Multi-omics analysis including metagenomics, untargeted metabolomics, and targeted short-chain fatty acids (SCFAs) analysis, were used to compare the structural differences in gut microbiota between the two groups and screen for signature differential bacterial species. Plasma levels of histamine and histidine decarboxylase were measured by ELISA to clarify the role of differential histidine metabolic pathway in the disease. Additionally, plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines (IL-1β, IL-6, IL-10, IL-17A, TNF-α) were detected by ELISA. The correlation between gut microbiota and inflammatory indicators was further analyzed. RESULTS: Compared to the healthy control group, the α-diversity of the gut microbiota in BLS patients was significantly reduced, with the microbial community structure exhibiting increased homogeneity. Beta diversity analysis revealed significant differences, suggesting that disease progression is associated with an overall imbalance in the gut microbiota and the deterioration of its specific structural composition. At the phylum level, the abundances of Actinomycetota, unclassified_d_Viruses, and Fusobacteriota were significantly increased in the gut microbiota of BLS patients compared to the control group, while the abundances of Bacillota and Pseudomonadota were significantly decreased. Further analysis revealed that, compared to the control group, the generic abundance of Enterococcus was significantly increased, while the proportions of Blautia, Faecalibacterium, Ruminococcus, Agathobacter, Roseburia, Clostridium, Eubacterium, Alistipes and Anaerobutyricum were significantly decreased. At the species level, the abundances of Enterococcus sp and Enterococcus-faecium were increased, whereas Blautia sp, Ruminococcus sp, Faecalibacterium sp, Faecalibacterium prausnitzii, Agathobacter rectalis, Eubacterium sp, Agathobacter sp, and Roseburia sp were decreased. Furthermore, untargeted metabolomics revealed that metabolites were enriched in the histidine metabolic pathway, and the levels of SCFAs including butyrate, isobutyrate, valerate, and 4-methylvalerate in the intestinal contents were reduced in BLS. Functional KEGG profiling revealed that key KOs involved in butyrate synthesis (e.g., K00074, K00172, K01640) and transport were globally downregulated in the patient group, whereas histidine decarboxylase KOs (K01693, K11755, K19787) that convert histidine to pro-inflammatory histamine were significantly enriched. The loss of butyrate-producing symbionts led to SCFAs deficiency and mucosal barrier disruption, creating ecological niches for facultatively anaerobic Enterococcus, which further exacerbated local inflammation via proteolytic fermentation and histamine production. Compared with the control group, BLS patients showed decreased plasma levels of IL-10, while levels of IL-1β, IL-6, IL-17A, and TNF-α were increased, and LPS levels were elevated. In addition, significantly elevated plasma pro-inflammatory LPS levels in patients with BLS suggest disruption of intestinal integrity and permeability. Correlation analysis indicated a close relationship between gut microbiota and inflammation. CONCLUSION: BLS is associated with gut microbiota dysbiosis and alterations in microbial metabolites, which may be linked to inflammatory responses and histamine metabolism. The differential microbial taxa identified in this study could be developed into a stool-based non-invasive diagnostic panel to facilitate early differentiation of BLS from other spinal disorders. Furthermore, restoring gut microbial balance through probiotic supplementation or dietary modulation may represent a promising adjunctive strategy to enhance the efficacy of standard antibiotic therapy and reduce disease recurrence.

Humans↗
PubMed2001

The balance between CD45RChigh and CD45RClow CD4 T cells in rats is intrinsic to bone marrow-derived cells and is genetically controlled.

The level of CD45RC expression differentiates rat CD4 T cells in two subpopulations, CD45RC(high) and CD45RC(low), that have different cytokine profiles and functions. Interestingly, Lewis (LEW) and Brown Norway (BN) rats, two strains that differ in their ability to mount type 1 and type 2 immune responses and in their susceptibility to autoimmune diseases, exhibit distinct CD45RC(high)/CD45RC(low) CD4 T cell ratios. The CD45RC(high) subpopulation predominates in LEW rats, and the CD45RC(low) subpopulation in BN rats. In this study, we found that the antiinflammatory cytokines, IL-4, IL-10, and IL-13, are exclusively produced by the CD45RC(low) CD4 T cells. Using bone marrow chimeras, we showed that the difference in the CD45RC(high)/CD45RC(low) CD4 T cell ratio between naive LEW and BN rats is intrinsic to hemopoietic cells. Furthermore, a genome-wide search for loci controlling the balance between T cell subpopulations was conducted in a (LEW x BN) F(2) intercross. Genome scanning identified one quantitative trait locus on chromosome 9 (approximately 17 centiMorgan (cM); log of the odds ratio (LOD) score 3.9). In addition, two regions on chromosomes 10 (approximately 28 cM; LOD score 3.1) and 20 (approximately 40 cM; LOD ratio score 3) that contain, respectively, a cytokine gene cluster and the MHC region were suggestive for linkage. Interestingly, overlapping regions on these chromosomes have been implicated in the susceptibility to various immune-mediated disorders. The identification and functional characterization of genes in these regions controlling the CD45RC(high)/CD45RC(low) Th cell subpopulations may shed light on key regulatory mechanisms of pathogenic immune responses.

Aging↗
PubMed2005

The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis.

INTRODUCTION: It is well established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. AIM: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. METHODS: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U(Prot)). Additional serum samples were stored at -80 degrees C for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). RESULTS: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U(Prot) (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U(Prot) (0-500 mg, 500-2000 mg, and > 2000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U(Prot), age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R2 = 33%). CONCLUSION: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.

Adult↗
PubMed1993

A tool to measure the change in health status of selected adult patients before and after intensive care.

If the effect of intensive care on the patient is to be fully assessed then the health status of patients before and after admission to ICU must be measured. The validity of a simplified system which can also use relatives, where necessary, as informants on the patients' pre-morbid health status has been evaluated. In a District General Hospital Intensive Care Unit a questionnaire based survey of 85 patients admitted over a period of eight months used a new specially-designed instrument and compared this with the Functional Limitations Profile (FLP) and the Perceived Quality of Life instrument (PQL). Relatives completed the health status questionnaire as soon as possible after the patient's admission and patients completed a suitably modified version at discharge from ICU. Patients were sent the FLP, PQL and modified health status questionnaire six months and one year after discharge. Questionnaires were completed by 59 paired relatives and patients. Questions were answered in the same way by relatives and patients; 42 of the 59 pairs of results were in agreement within two points of better or worse health. The closest responses were provided by wives in daily contact with their partner. At six months post ICU discharge, 49 patients completed the follow-up questionnaires, 12 patients had died and three were too confused to co-operate. Twenty-one patients (25%) were lost to follow-up. At one year post ICU discharge, 43 patients completed the follow-up questionnaires, one other patient had died and three still remained confused.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[The effect of the instructional profile in secondary schools on the body functional status of the pupils].

The main point of a lyceum is specialized education. The features of its educational process were studied by 6 profiles: medical, humanitarian, physicomathematical, chemobiological, technical, and commercial. The impact of either profile on the functional status of 2627 children was also examined. Study at the chemobiological, technical, and physicomathematical lyceums was shown to exert an unfavourable influence on the children's health.

Adaptation, Physiological↗
PubMed1984

P & T Committee roundtable discussion: Great Lakes region. Part II.

A series of regional roundtable discussions regarding the successful operation of Pharmacy and Therapeutic (P & T) Committees has been conducted by Hospital Formulary. Representation from private hospitals, university and teaching hospitals, as well as Veterans Administration Medical Centers has been achieved to ensure that different aspects of P & T Committee performance are demonstrated. Issues such as committee profile, constituency, function, and mechanics are discussed, as are criteria for establishing a successful formulary within an institution. The sessions were taped and the edited transcription is provided in the following article.

Great Lakes Region↗
PubMed1984

P & T Committee roundtable discussion: Eastern region. Part I.

A series of regional roundtable discussions regarding the successful operation of Pharmacy and Therapeutics (P & T) Committees has been conducted by Hospital Formulary. Representatives from private hospitals, university and teaching hospitals, as well as Veterans Administration medical centers discuss committee profile, constituency, function, mechanics, and criteria for establishing a successful formulary within an institution. The sessions were taped, and the edited transcription is provided in the following article.

Hospitals↗
PubMed1984

P & T Committee roundtable discussion: Eastern region Pt. II.

A series of regional roundtable discussions regarding the successful operation of Pharmacy and Therapeutics (P & T) Committees has been conducted by Hospital Formulary. Representatives from private hospitals; university and teaching hospitals, as well as Veterans Administration medical centers have participated to ensure that different aspects of P & T Committee performance are demonstrated. issues regarding committee profile, constituency, function, and mechanics are discussed, as are criteria for establishing a successful formulary within an institution. The sessions were taped, and the edited transcription is provided in the following article.

Cost Control↗
PubMed1999

Possibilities and limitations in the functional use of medical practice profiles.

The first use of medical practice profiles in the Belgian healthcare organization goes back to 1980 with the creation of practice pattern evaluation at the National Institute of Health and Invalidity Insurance (RIZIV). Since then, detailed information on the provision and on the utilization of healthcare has become increasingly important in the planning, budgeting and financing of the nation healthcare. The RIZIV uses practice profiling predominantly as a means to control aberrant prescription (e.g. clinical chemistry, medical imaging, pharmaceuticals) and provision of care (diagnostic tests). In 1991, the Federal Ministry of Health started using data on diagnosis and medical performance for hospital admissions in order to adapt the per diem price and the yearly quotum of admission days attributed to each hospital. At the level of the health insurer (sickness funds) there is growing interest to share the information derived from the extremely detailed patient claims for reimbursement of intramural and ambulatory care. These billing data allow the evaluation of medical care provision per physician, per hospital or provision center and per patient for a given period of time. The lack of specific diagnosis indication restricts mainly the use of these data as medical performance parameter to surgical procedures. The purpose of this profile information for the health insurer is to point to the physician the important medical practice variability in identical clinical situations in order to stimulate the design and implementation of practice guidelines and reduce aberrant differences in practice patterns. The use of medical practice profiles, in close collaboration of insurers and providers is considered extremely valuable as a means to improve the quality of healthcare provision.

Ambulatory Care↗
PubMed2000

Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival.

The chemokine stromal cell-derived factor-1 (SDF-1), and its receptor, CXCR-4, have been implicated in the homing and mobilization of human CD34(+) cells. We show here that SDF-1 may also be involved in hematopoiesis, promoting the proliferation of human CD34(+) cells purified from normal adult peripheral blood (PB). CXCR-4 was expressed on PB CD34(+) cells. The amount of CXCR-4 on PB CD34(+) cells was 10 times higher when CD34(+) cells were purified following overnight incubation. CXCR-4 overexpression was correlated with a primitive PB CD34(+) cell subset defined by a CD34(high) CD38(low)CD71(low)c-Kit(low)Thy-1(+) antigenic profile. The functional significance of CXCR-4 expression was ascertained by assessing the promoting effect of SDF-1alpha on cell cycle, proliferation, and colony formation. SDF-1 alone increased the percentage of CD34(+) cells in the S+G(2)/M phases and sustained their survival. In synergy with cytokines, SDF-1 increased PB CD34(+) and CD34(high)CD38(low) cell expansion and colony formation. SDF-1 also stimulated the growth of colonies derived from primitive progenitors released from quiescence by anti-TGF-beta treatment. Thus, our results shed new light on the potential role of this chemokine in the stem cell engraftment process, which involves migration, adhesion, and proliferation. Furthermore, both adhesion-induced CXCR-4 overexpression and SDF-1 stimulating activity may be of clinical relevance for improving cell therapy settings in stem cell transplantation.

Adult↗
PubMed2000

P53 regulation and function in normal cells and tumors.

Mechanisms to protect organisms from the consequences of DNA damage include the tumor suppressor p53 pathway. p53 protein binds specifically to a DNA consensus sequence to induce growth inhibitory genes or nonspecifically to damaged sites leading to DNA repair or apoptosis. While p53 protein is susceptible to post-translational modifications and binding to other proteins, few of the modifications or associations have been demonstrated in the context of the cell. We used a novel, sensitive DNA binding assay to examine p53 proteins in lysates prepared from cells responding to DNA damage. Non-transformed progenitor keratinocytes exhibited rapid and sustained induction of activated p53 protein binding to the consensus sequence, correlated with sustained induction of a downstream target gene, the cyclin-dependent kinase inhibitor p21. Binding to a mismatched DNA probe was transient and correlated with total p53 protein in the lysate, suggesting that most or all of the endogenous p53 proteins induced after damage were capable of mismatched DNA binding. Squamous cell carcinoma (SCC) derivates showed defects in induction p53 protein after DNA damage and disproportional losses in DNA binding, compared to total p53 protein steady state levels, along with increased NDN2/p53 association. Maximum induction of endogenous p53 protein binding to the mismatched probe correlated with transcription-independent induction of apoptosis. We suggest a model in which activated forms of p53 carry out transcription-dependent functions in growth arrest and DNA repair which may vary by cell type, while most or all wild type forms of p53 are capable of binding to damaged DNA. p53 protein loss of binding to damaged DNA causes failure of cells to trigger apoptosis and may lead to resistance to chemotherapy. Implications for new directions in therapeutics include functional molecular profiling of individual patient tumors for p53 DNA binding to predict treatment response better than mutational analysis alone and targeted activation of p53 DNA damage binding in tumor cells for increasing their sensitivity to chemotherapy.

Apoptosis↗