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Biomedical subjects

D Gottlieb

Publications and source records attributed to D Gottlieb.

At least 19 recordsLinked to original sources

The influence of social support and perceived control on handicap and quality of life after stroke.

It has been suggested that external factors, such as perceived control of life and social support, influence the interactions of impairment, disability and handicap in the WHO model. Therefore, we assessed the effect of these two factors on the relationships between disability, handicap and quality of life in patients recovering from stroke. One hundred individuals, retrospectively and randomly selected from participants in an inpatient stroke rehabilitation program, were tested one year after discharge, using the Functional Independence Measure, the London Handicap Scale, the Life Satisfaction Assessment, the Tel-Aviv Social Support Instrument, and the Perceived Stress Scale. Impairment, disability, handicap and quality of life after stroke correlated positively and significantly with each other. Significant moderation of the influence that disability exerts on handicap was affected by perception of control, and by the influence of handicap over quality of life by social support. Thus, external factors can cause inconsistent interactions between components of the WHO model. Patient outcome may be improved if such factors are considered.

Aged↗

A telephone-linked computer system for COPD care.

The current revolution in communications technology provides an opportunity for novel approaches to management of medical illness. As economic imperatives lead to a progressive reduction in the time that health-care providers spend with their patients, computerized, telephone-linked communication systems offer an inexpensive, widely available alternative with which patients and providers can maintain contact. Such systems may be particularly useful for providing ongoing monitoring and education of patients with chronic illnesses such as COPD. In this article, we describe the general application of telephone-linked communication systems in the health-care setting. We then present in detail one such system, which provides telephone-linked care for COPD (TLC-COPD). The operation of the system is described, as are its theoretical underpinnings in social learning theory. A randomized clinical trial currently is being performed to study the effects of the TLC-COPD system. The rationale for expected improvements in disease control and quality of life, and for a reduction in acute health-care utilization, is discussed.

Algorithms↗

Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans--does it have an abettor role in oxalate, and calcium oxalate crystallization?

The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known.

Administration, Oral↗

Geographic heterogeneity of cellular characteristics of acute myeloid leukemia: a comparative study of Australian and Japanese adult cases.

We assessed a large number of adults (368 from Australia and 494 from Japan) with de novo acute myeloid leukemia (AML) to define the biological differences between the two populations. In this study, AML was classified using the French-American-British (FAB) criteria into seven groups (M1-M7). M2 was more common in Japan than in Australia, whereas M4 occurred more frequently in Australia than in Japan. Other FAB subtypes were evenly distributed. Cytogenetically, Japanese M2 displayed a higher frequency of t(8;21) than Australian (33.1% vs 15.3%, P < 0.05). The t(15;17), inv/del(16), 11q23 aberrations and 5/7/8 abnormalities were seen at similar frequencies. Immunophenotypically, Japanese M4/M5 more frequently displayed CD13 and CD14 than Australian, whereas the stem cell markers, CD34 and HLA-DR were observed at a relatively higher rate in Australian M3 than in Japanese M3. The B cell antigen, CD19 was more frequently seen in Japanese M2 than in Australian M2, but found more often in Australian M5 than in Japanese M5. In both populations, a close relationship was observed between the expression of CD19 and t(8;21). These findings suggest different biological characteristics of AML between the two populations, the main differences being generated by a higher frequency of t(8;21) chromosomal abnormality in Japanese AML. Leukemia(2000) 14, 163-168.

Acute Disease↗

On the direct Fourier method for computer tomography.

The paper considers the direct Fourier methods (DFM's) for reconstructing an image from its given X-ray projections. The main purpose here is to use concepts from numerical analysis to estimate the errors in the methods. We also suggest an alternative to the interpolations involved in the DFM's and estimate the number of terms involved. Realizing that one of the main reasons for the degradation of the quality of the reconstruction is the Gibbs phenomenon, we suggest a way to overcome this difficulty and give numerical evidence of its efficacy.

Algorithms↗

Like a terrorist.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

The DPL1 gene is involved in mediating the response to nutrient deprivation in Saccharomyces cerevisiae.

Sphingosine-1-phosphate is a sphingolipid metabolite involved in the regulation of cell proliferation in mammalian cells. The major route of sphingosine-1-phosphate degradation is through cleavage at the C, bond by sphingosine phosphate lyase. The recent identification of the first dihydrosphingosine/sphingosine phosphate lyase gene in Saccharomyces cerevisiae establishes that phosphorylated sphingoid base metabolism is conserved throughout evolution. The dpl1delta deletion mutant, which accumulates endogenous phosphorylated sphingoid bases, exhibits unregulated proliferation upon approach to stationary phase. The increased proliferation rate during respiratory growth was associated with failure to appropriately recruit cells into the G1 phase of the cell cycle. Several genes were found to be overexpressed or prematurely expressed during nutrient deprivation in the dpl1delta strain, including glucose-repressible genes and G1 cyclins. These studies implicate a role for DPL1 and phosphorylated sphingoid bases in the regulation of global responses to nutrient deprivation in yeast.

Aldehyde-Lyases↗

Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis.

The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted.

Calcium Oxalate↗

VLA-4 is involved in the engraftment of the human pre-B acute lymphoblastic leukaemia cell line NALM-6 in SCID mice.

Attachment of human pre-B leukaemic cells to human or murine bone marrow stromal cells in vitro is largely mediated by the beta1 integrin VLA-4 binding to VCAM-1. Cells subsequently migrate within the stroma, a process also involving VLA-4. A variant of the pre-B acute lymphoblastic leukaemia cell line NALM-6, designated 4A1, lacking expression of VLA-4, was generated by radiation-induced mutagenesis followed by several rounds of negative selection with immunomagnetic beads, fluorescence activated cell sorting and clonal expansion. In vitro assays using 4A1 cells showed reduced binding to, and migration under, the murine stromal line M2-10B4. Sublethally irradiated mice (n=19) with severe combined immunodeficiency were injected intravenously with NALM-6 cells. Animals developed signs of leukaemia with hind-limb paralysis at a median of 30 d (95% confidence interval 28-30). Although there were no gross abnormal findings at autopsy, histological analysis revealed extensive marrow replacement and focal liver infiltration with leukaemic blasts, which were confirmed to be of human origin by flow cytometry. 12 mice were injected with a similar number of cells from the VLA-4-negative variant cell line 4A1. Six mice developed signs of leukaemia after 43-74d, with the remaining six being free of signs of disease after > 100d (P<0.001). Mice in this group with leukaemia had a lower incidence of hind-limb paralysis and less leukaemic infiltration in the marrow, but in some cases had large tumour nodules elsewhere. After a single 500 microg intraperitoneal injection of anti-murine VCAM-1 monoclonal antibody (MK2.7), five additional mice were injected with an identical number of wild-type (VLA-4+) NALM-6. All animals developed signs of leukaemia after a similar period to those injected with wild-type NALM-6 only. These results demonstrate that the beta1 integrin VLA-4 is involved in the engraftment of the pre-B-cell leukaemic cell line NALM-6 in SCID mice, although the interaction with VCAM-1 is unlikely to be the sole explanation.

Animals↗

Antileukemic effects of rapid cyclosporin withdrawal in patients with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

The results of rapid tapering of Cyclosporin therapy in 7 patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in relapse after allogeneic bone marrow transplantation are reported. All patients had cytogenetically-documented relapse within 6 months of transplant, and were on oral Cyclosporin therapy. Rapid tapering of Cyclosporin resulted in moderately severe acute GVHD in 2 cases, and in extensive chronic GVHD in a further 2 patients (fatal in 1 case). An antileukemic effect was observed in 6 patients, with complete haematological and cytogenetic remission observed in all cases. The seventh patient did not respond, and died after infusion of donor leucocytes. Four of the responders remain in complete remission of CML 30 to 120 months after BMT. One patient died in remission of chronic GVHD, and one patient had a complete response lasting 5 months, but relapsed and died 13 months post transplant. Rapid withdrawal of Cyclosporin therapy appears to be an effective means of treatment of early relapse of CML after transplant, and is an alternative to the use of donor leucocyte infusions for those patients still receiving Cyclosporin at the time of relapse.

Adolescent↗

[Hospitalization of the elderly for stroke rehabilitation].

This is descriptive, longitudinal study of 400 elderly patients admitted for stroke rehabilitation to a geriatric department dedicated to this purpose. We present the demographic, medical, and impairment and disability characteristics on admission, and the outcome of rehabilitation. Mean stay was 54 days and 2/3 became independent and returned home. Functional score on admission was the best predictor of outcome, but age and social support were also significant.

Activities of Daily Living↗

Ultrastructural changes during adhesion and migration of pre-B lymphoid leukaemia cells within bone marrow stroma.

The ultrastructural changes in leukaemic cells on initial contact with, and during migration into, layers of bone marrow stroma in vitro were examined in a variety of types of acute leukaemia and leukaemic cell lines. Bone marrow fibroblasts (BMF) were grown on polycarbonate microporous membranes, and acute leukaemia cells added to cultures and allowed to adhere to BMF for variable periods of time before fixation. Acute lymphoblastic leukaemia (ALL) blasts showed rapid development of surface membrane microvilli on contact with BMF layers. ALL blasts, and the pre-B ALL cell line NALM-6, showed evidence of movement in to the BMF layer within 15-30 min, with intrusion of extended cytoplasic processes into gaps between BMF cytoplasm. ALL cells were frequently seen within the layers of fibroblasts after 30 min incubation, and had pronounced morphological changes, with pseudopodia and attenuated and elongated microvilli interdigitating with the surface of fibroblasts or with strands of extracellular matrix material. Changes were also noted in the surface membrane of BMF adjacent to ALL cells, with invagination of the cytoplasmic membrane and formation of micropits. In contrast to the migratory behaviour of pre-B ALL cells, migration was not observed with acute myeloid leukaemia cells or other leukaemic cell lines. These cells showed membrane activation, with variable degrees of microvillous formation, and in some cases insertion of pseudopodia into BMF layers, but migration was not observed. Ultrastructural immunogold labelling was carried out to determine the localization of leukaemic adhesion molecules and their ligands on BMF. This demonstrated that beta 1 integrins were largely localized to the contact surfaces of both ALL blasts and fibroblasts, with VCAM-1 expressed only on the surface of BMF. These observations confirm the specificity of migratory behaviour for pre-B leukaemic cells, and indicate that a complex pattern of surface and intracellular events mediate this process, including the expression of beta 1 integrins and VCAM-1 at the sites of insertion of leukaemic cells between fibroblast margins.

Acute Disease↗

Parents' perceptions of children's worries in a changing world.

The nature and intensity of worries that preadolescent children experience and the extent to which parents are aware of their children's concerns were examined. Questionnaires with three subscales (Physical Harm, Daily Life Matters, and Global Issues) were filled out by 89 6th graders and their parents. Parents underestimated the overall degree to which children worry, and they tended to believe that their children worried most about daily life matters, such as grades and popularity; children were in fact least worried about daily life matters and most worried about global issues, such as pollution and starvation. Both child and parent gender differences were found.

Adaptation, Psychological↗

Common sense, insight, and neuropsychological test performance in schizophrenia patients.

We report an exploratory study examining the interrelationships among common sense, insight into psychosis, and performance on a battery of neuropsychological tests in 32 patients with schizophrenia evaluated at the time of discharge from involuntary hospitalization at a State psychiatric hospital. Common sense, as measured by the Social Knowledge Questionnaire, was associated with better performance across tests measuring parietal lobe functioning and vocabulary. In addition, patients with more common sense were more likely to say that they were ill and needed treatment. A global measure of insight, the Insight and Treatment Attitudes Questionnaire (ITAQ), was related to performance on a test of left parietal lobe function. However, the responses to the ITAQ item that may best reflect current awareness of mental illness in patients at the time of discharge ("After you are discharged, is it possible you may have mental problems again?") were related to performance on tests of the functioning of the prefrontal lobes and the right and left parietal lobes. These results add to the growing evidence that some of the deficits in awareness of illness among patients with schizophrenia are related to the neuropsychological dysfunction commonly seen in patients with this disorder.

Adult↗

Validation of the 50 ml3 drinking test for evaluation of post-stroke dysphagia.

Aspiration pneumonias are frequent complications of cerebrovascular accidents (CVA). They occur mainly in patients suffering from swallowing disorders following the CVA. These patients can be diagnosed using a bedside swallowing evaluation. This evaluation is based on observation of some components of the oral and pharyngeal stages of the swallowing process and on a drinking test of 50 ml3 of clear liquids. Changing the mode of swallowing and the consistency of the diet according to the swallowing evaluation following CVA can reduce significantly the frequency of aspiration pneumonias. In our patient cohort, consisting of 180 patients admitted for stroke rehabilitation, aspiration pneumonias occurred in 10% and swallowing disorders were found in 28%. The administration of a structured swallowing evaluation was associated with a gradual reduction of frequency of pneumonia from 16% in the first group of 60 patients to 3% in the last group of 60 patients or, if considering only patients suffering from dysphagia, from 27% in the first group of patients to none in the last group of patients.

Aged↗

Long-term survival and proliferation of precursor-B acute lymphoblastic leukemia cells on human bone marrow stroma.

Leukemic cells frequently persist in the bone marrow of patients treated for acute lymphoblastic leukemia (ALL), and may regrow to produce relapse. We have used a long-term co-culture system to analyze the interaction of ALL blasts with components of the marrow microenvironment. Blast cells from 10 cases of precursor-B ALL were cultured on allogeneic human bone marrow stromal layers at 37 degrees C in microtiter wells, and replated when stroma showed evidence of deterioration. Leukemic cells from seven of 10 cases showed evidence of survival and proliferation beyond 30 days in culture, while in three cases there was a progressive decline in the number of viable leukemic cells by 7-21 days. Two cases continued to proliferate for 149 to 332+ days, while five underwent senescence after 34-52 days. In the two cases with long-term proliferation, the leukemic identity of the cells was confirmed by immunophenotyping, cytogenetics, and demonstration of clonal immunoglobulin gene rearrangements. Evidence of selection of leukemic subclones was seen in two cases, with immumophenotypic evidence of loss of CD10 and CD34 antigens, and acquisition of CD20 and surface mu chain. The leukemic cells in these cases grew either in clumps attached to the surface of the stroma, or as'cobblestone areas' beneath the stromal cells. Survival and growth of two evaluable cases was dependent on the continuing presence of stromal cells in the culture system. In one case, direct contact with stroma was shown to be necessary to main- tain viability, while blast cells from the other case survived equally well when separated from the stroma by a 0.4-micron pore size microporous membrane. These results indicate that leu- kemic cells from the majority of cases of precursor-B ALL are able to persist and undergo proliferation in vitro in the presence of normal marrow stroma. This process appears dependent on either direct cell-cell contact, or on diffusible factors derived from the stroma. The availability of ALL cells capable of indefinite proliferation under these conditions will allow further analysis of the mechanisms mediating leukemic cell proliferation.

Adolescent↗

[Reduction in frequency of pneumonia after stroke, following programmed swallowing evaluation].

Aspiration pneumonia is a frequent complication of cerebrovascular accidents (CVA). It occurs mainly in those with post-CVA swallowing disorders, which can be diagnosed by bedside swallowing evaluation. Evaluation is based on observation of components of the oral and pharyngeal stages of swallowing a drink of 50 ml of clear liquid. Changing the consistency of the diet and the mode of swallowing, following its evaluation, can reduce significantly the frequency of post-CVA aspiration pneumonia. In 180 patients admitted for stroke rehabilitation, aspiration pneumonia occurred in 10% and swallowing disorders were found in 28%. Planned swallowing evaluation followed by the above regimen was associated with a gradual reduction of pneumonia from 16% in the first group of 60 patients to 3% in the second group of 60; and of patients with dysphagia, from 27% in the first group to none in the second.

Cerebrovascular Disorders↗