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Biomedical subjects

D Gottlieb

Publications and source records attributed to D Gottlieb.

At least 37 records · Page 2Linked to original sources
PubMed1998

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↗
PubMed1997

[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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

[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↗
PubMed1995

Diffuse alveolar haemorrhage associated with microangiopathy after allogeneic bone marrow transplantation.

Microangiopathic disease and diffuse alveolar haemorrhage (DAH) are uncommon serious complications of bone marrow transplantation (BMT), but an association between these two conditions has not been previously recognised. We report 4 patients in whom these two complications occurred after allogeneic BMT for haematological malignancy. The patients were 16-39 years of age, and received transplants for acute myeloid leukemia, chronic myeloid leukemia and non-Hodgkin's lymphoma (n = 2). Donors were HLA-identical siblings (n = 3), and a matched unrelated volunteer. The patient with AML was receiving a second transplant for relapse 3 years after her first BMT, and was prepared with busulphan and melphalan; other patients received total body irradiation and cyclophosphamide. Microangiopathy occurred 20-48 days after BMT, and was associated with renal impairment in all cases, and mental confusion in 3. Cyclosporin levels were in the toxic range in 2 cases. DAH occurred 18-55 days after BMT, in 3 cases 2-7 days after the onset of microangiopathy, but preceding it by 14 days in the other case. Patients were treated with fresh frozen plasma, plasma exchange, supplemental oxygen and ventilation in 2 cases. Two patients died of progressive respiratory failure, while 2 patients recovered with evidence of continuing microangiopathic disease, and died of myocardial infarction or fungal infection. We report an association between microangiopathic disease and DAH in these BMT patients, and suggest that damage to the pulmonary vascular endothelium may be the common pathophysiological event, although no specific causative factor could be identified.

Acute Disease↗
PubMed1994

Migration of acute lymphoblastic leukemia cells into human bone marrow stroma.

Most cases of acute lymphoblastic leukemia (ALL) arise from malignant transformation of B-cell precursors in the bone marrow. Recent studies have shown that normal and leukemic B-cell precursors bind to bone marrow stromal cells through the beta-1 integrins VLA-4 and VLA-5, thereby exposing early lymphoid cells to regulatory cytokines. It has been recently reported that the pre-B cell line NALM-6 is capable of migrating under layers of murine stromal cells in vitro (Miyake et al. J Cell Biol 1992;119:653-662). We have further analyzed leukemic cell motility using human bone marrow fibroblasts (BMF) as a stromal layer. The precursor-B ALL cell line NALM-6 rapidly adhered to BMF, and underwent migration or tunneling into BMF layers within 5 h, as demonstrated by light and electron microscopy, and confirmed by a chromium-labeling assay. Migration was also observed with the precursor-B ALL lines Reh and KM-3, with a T leukemia line RPMI-8402, the monocytic line U937, and the mature B line Daudi. In contrast, mature B (Raji), myeloid (K562, HL-60), and T lines (CCRF-CEM, MOLT-4) did not migrate. When cases of leukemia were analyzed, BMF migration was largely confined to precursor-B ALL, occurring in eight of 13 cases tested. Of other types of leukemia, migration was observed in one of four cases of T-ALL, but no evidence was seen in six acute myeloid leukemias and two patients with chronic lymphocytic leukemia. Only minimal migration into BMF was observed with purified sorted CD10+ CD19+ early B cells from normal adult marrow, while normal mature B lymphocytes from peripheral blood did not migrate. ALL migration was inhibited by monoclonal antibodies to the beta sub-unit of the VLA integrin family, and by a combination of antibodies to VLA-4 and VLA-5. Partial inhibition was also observed when leukemic cells were incubated with antibodies to VLA-4, VLA-5, or VLA-6 alone. In contrast, treatment of stromal cells with antibodies to vascular cell adhesion molecule or fibronectin (ligands of VLA-4 and VLA-5) did not prevent leukemic cell migration. These results indicate that ALL cells are highly motile and capable of rapid migration within marrow stroma, an effect largely mediated by VLA-4 and VLA-5. In the case of precursor-B ALL, this process may reflect a homing mechanism to areas of selective growth advantage within the bone marrow microenvironment.

Antigens, CD↗
PubMed1992

Mirror movements in the alien hand syndrome. Case report.

The alien hand syndrome has been associated with different descriptions of abnormal motor behavior. We report on two patients with transient left hemiparesis who remained with limb apraxia and were particularly impaired by a variety of involuntary skilled movements of their apractic limb. After the report and a review of the literature, we discuss the presence of one type of abnormal movement observed in this syndrome. These movements resemble the mirror movements seen in the normal development of motor control and in some pathologic conditions later. Their appearance in the alien hand syndrome seems to demand both intrahemispheric and interhemispheric motor pathway damage.

Apraxias↗
PubMed1992

The unidirectionality of cerebral polyopia.

Polyopia, visual perseveration in space, has been associated with seizure activity, afterimage formation, and the presence of visual field defects. It can be interpreted both as a positive and a negative visual phenomenon. A patient with polyopia associated with the acute onset of hemianopsia is presented. The phenomenon has been investigated objectively with a simple procedure. The polyopia was highly correlated to movement of the eyes into the hemianoptic visual field and to increased contrast but not duration of the stimulus. This type of polyopia could be the result of incomplete visual processing due to poor visuospatial localization in a hemianopic field.

Aged↗