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Biomedical subjects

E Feldman

Publications and source records attributed to E Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy.

PURPOSE: To evaluate whether intensive chemotherapy followed by peripheral stem-cell (PSC) collections during early hematopoietic recovery results in a higher percentage of diploid cell collections in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Fifty-five adults with Ph-positive CML received intensive chemotherapy with daunorubicin and high-dose cytarabine (ara-C) (DAUNO-HDAC; 26 patients) or fludarabine, high-dose ara-C, and mitoxantrone (FAM; 29 patients). Collections of the peripheral mononuclear cells were initiated when the WBC count was > or = 0.8 x 10(3)/microL. Simultaneous peripheral and marrow samples were subjected to cytogenetic studies. RESULTS: Thirty-eight of 55 patients (69%) were able to undergo the PSC collections. The rate of collection was higher in chronic phase (26 of 30 patients; 87%) than in accelerated (11 of 17; 65%) and blastic phases (1 of 8; 12%). Among the 30 patients in chronic phase, cytogenetic analyses of PSC showed cytogenetic responses (Ph-positive < 95%) in 60%, which were major (Ph < 35%) in 43% and complete (Ph = 0%) in 27%. Seven of 19 patients with simultaneous studies (37%; 23% of total) had a significantly lower percentage of Ph-positive cells in the peripheral collection compared with the marrow collection; one had the reverse phenomenon (5%; 3% of total). Cytogenetic responses were modest in both peripheral and marrow collections in CML accelerated and blastic phases. Myelosuppression-associated complications were frequent, resulting in febrile episodes in 76% of patients. CONCLUSION: PSC collection during early hematopoietic recovery from intensive chemotherapy allowed the collection of diploid-rich stem cells, mostly in chronic-phase CML. The approach could be used for in vivo purging before autologous stem-cell transplantation (ASCT).

Adolescent↗
PubMed1994

Apoptotic cell death during treatment of leukemias.

The apoptosis-associated DNA strand breaks were detected in situ, in individual leukemic cells in peripheral blood and bone marrow of over 110 patients with different types of leukemia (ALL, AML, CML in blastic crisis, APL), prior to and during routine chemotherapy. The DNA strand breaks were labeled with digoxigenin- or biotin-conjugated dUTP in the reaction catalyzed by exogenous terminal deoxynucleotidyl transferase, and the cells, counterstained for DNA, were analyzed by bivariate flow cytometry. The proportion of cells with DNA strand breaks prior to therapy, most likely reflecting spontaneous apoptosis, varied from 0.1 to 16%, but in the large majority of cases was below 3%. Administration of drugs of different classes, which included DNA topoisomerase I (Topotecan) and II (mitoxantrone, VP-16) inhibitors, antimetabolite (ara-C) or microtubule poison (Taxol), all triggered the appearance of cells with extensive DNA breakage, typical of apoptosis, to up to 80%. The peak of the response, measured as maximal percent of cells with DNA strand breaks, which varied between individual patients by as much as factor 10, was generally seen between 8 to 24 h after the initial administration of DNA topoisomerase inhibitors, and somewhat later (48-72 h) during the response to Taxol or ara-C. Thus, the data show that the response to treatment with a variety of drugs, in terms of induction of apoptosis, can be conveniently measured by the present method. The prognostic value of the apoptotic index, before, as well as during treatment, is being estimated for each type of leukemia, in the ongoing prospective studies.

Antineoplastic Agents↗
PubMed1994

Prospective randomized comparison of intravenous versus subcutaneous administration of radioiodine for treatment of hyperthyroidism in cats.

One hundred twenty cats with hyperthyroidism were treated with radioiodine (131I); 60 cats were administered radioiodine SC, and 60 cats were administered radioiodine IV. Before treatment, radioactive tracer studies were performed on each cat to determine peak radioactive iodine uptake and effective half-life. These data were used to calculate the dose of radioiodine that would have to be given to each cat to deliver 150 Gy to the thyroid tissue. The 2 groups of cats were similar with regard to age, tracer study results, and radioiodine dose. Mean estimated thyroid mass was larger for cats treated IV, but mean serum thyroxine concentration was higher for cats treated SC. Route of administration did not affect thyroidal uptake of radioiodine. However, radiation exposure of personnel was significantly lower with SC administration than with IV administration, even when IV catheterization was performed Eighty-five percent of cats treated IV and 84% of cats treated SC were euthyroid 4 years after treatment. Six percent of the cats became hypothyroid after treatment. When compared with IV administration, SC administration of radioiodine appeared to be as effective for treatment of hyperthyroidism, safer to personnel, and less stressful to the cats.

Animals↗
PubMed1994

An investigation into the psychoanalytic concept of envy.

The authors describe the evolution of the concept of envy since Freud's first account of penis envy. Influenced by Abraham, Klein stressed the importance of envy 'lato sensu', turning it into a major issue in both psychoanalytic theory and practice. Her final proposition that envy is a direct expression of the death instinct was criticised from many quarters. These critiques, as well as her follows' contributions to the theme, are examined. Although the Kleinian conceptualisation contributed greatly both to psychoanalytic theory and practice, the time has come to re-evaluate it in the light of later clinical and theoretical developments. The authors consider envy to be a complex feeling, not an impulse or a drive derivative. The object of envy is not the good object but the omnipotent-idealised object, thought to have qualities felt by the infant as unattainable. The newborn's mind is overwhelmed with a sense of loss that cannot be mourned. The coping is done through a process called Precocious Mourning, at a stage in which there is barely any self-object differentiation, leading to sensations that the authors call precursors of envy. Envy (proper) is a universal feeling, whose strength depends on subject-object (complementary series) interactions occurring when differentiation is under way.

Adaptation, Psychological↗
PubMed1994

Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in patients with refractory or relapsed lymphomas.

Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13 patients with Hodgkin's disease, were treated with a combination of high dose Ara-C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2 continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to 750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky performance status was 80 (range 60-100). Patients treated included: primary refractory six, first relapse 14, > first relapse seven, and resistant relapse six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23 patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in patients who were refractory to previous chemotherapy and occurred in all sites. Toxicity was tolerable with most patients not requiring hospitalization following chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the other of a sudden death. Severe mucositis was not observed. High dose etoposide based salvage chemotherapy offers a greater probability of response than lower dose etoposide. This regimen is well tolerated and can be administered with relatively brief hospitalization.

Adult↗
PubMed1993

Long-term reversal of diabetes by the injection of immunoprotected islets.

The intraperitoneal injection of insulin-producing islets immunoprotected by an alginate-poly(amino acid) membrane is a potential method of reversing diabetes without the need for lifelong immunosuppression. Previous attempts to demonstrate this technology in large animals have failed, preventing application in humans. We have determined that key factors responsible for these past failures include cytokine (interleukins 1 and 6 and tumor necrosis factor) stimulation by mannuronic acid monomers from alginate capsules with weak mechanical integrity, which results in fibroblast proliferation. With this insight, we formulated mechanically stable microcapsules by using alginate high in guluronic acid content and report prolonged reversal of diabetes in the spontaneous diabetic dog model by the intraperitoneal injection of encapsulated canine islet allografts. Euglycemia, independent of any exogenous insulin requirement, was noted for up to 172 days. Graft survival, evidenced by positive C-peptide release, was noted for as long as 726 days in a recipient receiving a single injection of immunoprotected islets. Histological evidence of viable islets retrieved from the peritoneal cavity 6 months posttransplant confirmed the biocompatibility and immunoprotective nature of this capsule formulation. The finding that intraperitoneal injection of alginate-immunoprotected islets, a minimally invasive surgical procedure, is effective in prolonged (> 1 year) maintenance of glycemic control, without the need for lifelong immunosuppression, may have significant implications for the future therapy of type I diabetes in humans.

Alginates↗
PubMed1993

Temporal lobe surface area measurements on MRI in normal and dyslexic readers.

In a neuroanatomical study of dyslexia, measurements were made of the superior surface of the temporal lobe (SSTL) on MRI scans in a sample of 17 dyslexics and 21 non-dyslexic subjects. Both anterior and posterior halves of the SSTL area showed significant leftward asymmetry in non-dyslexics, but showed symmetry in dyslexics. The total SSTL area showed greater leftward asymmetry in non-dyslexics than in dyslexics. The dyslexics also revealed a significant correlation (r = 0.69, P = 0.005) between Woodcock-Johnson Passage Comprehension scores and posterior SSTL asymmetry, such that those with higher scores had more leftward asymmetry. This suggests that among dyslexics the direction of SSTL asymmetry may serve as a risk factor and/or a marker for the severity of reading comprehension problems.

Adolescent↗
PubMed1993

Refining the genetic location of the gene for X linked hydrocephalus within Xq28.

The most common inherited form of hydrocephalus, X linked hydrocephalus (HSAS), is characterised by mental retardation, adducted thumbs, and spastic paraplegia. Genetic analysis has mapped the locus for HSAS to subchromosomal band Xq28 within a region of approximately 2 megabases of DNA. In order to refine the location of the disease gene we have conducted genetic linkage analysis with Xq28 marker loci in four additional HSAS families. A lod score of 4.26 with polymorphic marker DXS52 (St14) confirms the linkage of HSAS to Xq28. Identification of a recombination event between the HSAS gene and Xq28 loci F8C and DXS605 (2-19) reduces the size of the interval likely to contain the disease locus to about 1.5 megabases, the distance between DXS605 and DXS52. The locus for neural cell adhesion molecule, L1CAM, maps within this interval and therefore represents a candidate gene for HSAS.

Adolescent↗
PubMed1993

Adult familial dyslexia: a retrospective developmental and psychosocial profile.

This study investigated the developmental, demographic, educational, and psychosocial outcome of 36 adults with third-generation familial dyslexia. Control subjects were 44 unaffected age-matched family members. Compared with control subjects, those with familial dyslexia 1) had similar incidences of perinatal complications, left-handedness, and right-left confusion but reported more early speech/language problems; 2) performed worse in reading and spelling but had similar educational achievement; 3) were more likely to report depression/anxiety symptoms and to have attention-deficit disorder with hyperactivity; and 4) were similar in medical history, marital stability, and mean income. Data suggest that, despite continued isolated reading deficits, carefully selected subjects with adult familial dyslexia do not show the previously described downward course of the learning-disabled population.

Adult↗
PubMed1992

Prognostic significance of elevated serum beta 2-microglobulin levels in adult acute lymphocytic leukemia.

PURPOSE: Elevated serum beta-2 microglobulin (beta 2M) levels are associated with poor prognosis in several lymphoproliferative disorders including multiple myeloma and lymphoma. Their prognostic relevance in acute lymphocytic leukemia (ALL) is unknown. We analyzed the associations of serum beta 2M levels at diagnosis with pretreatment characteristics and with prognosis in adult ALL. PATIENTS AND METHODS: One hundred fifty-nine adults with newly diagnosed ALL were investigated. Serum beta 2M levels were determined at diagnosis, on fresh peripheral blood samples, using a radioimmunoassay, the Pharmacia beta 2 Micro RIA (Pharmacia Diagnostics, Uppsala, Sweden). Statistical correlations were assessed by standard methods, and further independent prognostic value of serum beta 2M was determined by multivariate analysis. RESULTS: Patients with beta 2M levels of 4.0 mg/L or above had a lower complete response rate (61% versus 80%; p = 0.02), a significantly worse survival (p < 0.01), and a significantly higher association with development of central nervous system (CNS) leukemia (p < 0.01). High beta 2M levels were more common among patients with older age, with elevated creatinine, bilirubin, and alkaline phosphatase levels, with low albumin levels, and with B-cell disease. Multivariate analysis for survival indicated the beta 2M level to be an independent prognostic variable (after adjusting for pretreatment creatinine level and age). The evaluation of beta 2M levels within low- and high-risk groups for CNS disease suggested an association of elevated beta 2M levels with a worse incidence of CNS disease in the high-risk patients. CONCLUSION: Monitoring serum beta 2M levels may provide significant prognostic information in adults with ALL and should be included in their pretreatment evaluation. Its importance in childhood ALL requires investigation.

Adult↗
PubMed1992

Alzheimer Disease Assessment Scale: a subtest analysis.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 Alzheimer patients, 52 elderly controls, and 80 controls between age 7 and 54 years. The Alzheimer group was categorized into different severity levels of dementia based on MMSE scores: very mild (> or = 24), mild (> or = 20), moderate (10-19), and severe (0-9). All 11 ADAS Cognitive subtest scores for the mild, moderate, and severe dementia groups were statistically worse than the elderly control group. This was also the case for the very mild group, except for Naming, Commands, Constructional Praxis, and Ideational Praxis. In terms of magnitude of effect, memory and spontaneous language items were the earliest indicators on the ADAS, while praxis, commands, and naming items were only sensitive later in the course of the disorder. The best single indicators of progression throughout the severity continuum of dementia (i.e., from normal to severe) were the Orientation subtest, the ADAS Cognitive score, and the ADAS Total score. The ADAS Noncognitive subtests generally did not show the progression with increasing dementia that was evident on the ADAS Cognitive subtest. Differences in educational level had no statistically significant effects on any of the ADAS subtest scores, and age differences were few and small in magnitude. The differential rate of decline of the various ADAS subtests appears to reflect both the changing pattern of cognitive impairments as a function of severity of DAT and also to some extent the psychometric limitations of some of the subtests.

Aged↗
PubMed1992

Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets.

Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism(s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6 +/- 0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n = 3) or as microencapsulated islet allografts (n = 7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose failing from 304 +/- 117 to 116 +/- 72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6 +/- 0.4 to 2.6 +/- 0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63-172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.

Animals↗
PubMed1992

Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine.

PURPOSE: To evaluate the efficacy of interferon-alpha (IFN-A) and low-dose cytarabine (ara-C) combination chemotherapy in patients with chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Sixty patients with advanced phases of Philadelphia chromosome (Ph)-positive CML received combination therapy with IFN-A 5 x 10(6) U/m2 daily, and low-dose ara-C 15 mg/m2 daily for 2 weeks every 4 weeks until remission, then for 1 week every month as maintenance. Forty patients were in late chronic-phase CML, and 20 were in accelerated-phase CML (16 with clonal evolution only, four with other criteria). Their outcome was compared with 58 patients (39 late chronic-phase CML and 19 accelerated-phase CML) who had been previously treated with IFN-A alone in the same dose schedule. RESULTS: In late chronic-phase CML, patients receiving IFN-A plus ara-C had a better complete hematologic response (CHR) rate compared with those treated with IFN-A alone (55% v 28%; P = .02), a trend for better Ph suppression (15% v 5%; P = .13), and a longer survival (3-year survival rate 75% v 48%; P less than .01). These differences do not seem to be caused by imbalances in prognostic factors between the two treatment groups. In accelerated-phase CML, the addition of ara-C to IFN-A did not improve the response rate of treated patients, and the difference in survival was accounted for by different patient characteristics. Suppression of clonal evolution was observed in five patients (25%). Patients with clonal evolution as the only criterion for disease acceleration had a longer survival than those with other or additional accelerated-phase criteria (3-year survival rate 67% v 22%; P less than .01). CONCLUSION: The results with the combination of IFN-A plus ara-C in late chronic-phase CML are encouraging, and suggest the need for its evaluation in early chronic-phase CML.

Adult↗
PubMed1992

Alzheimer disease assessment scale: useful for both early detection and staging of dementia of the Alzheimer type.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 patients with dementia of the Alzheimer type (DAT) and 52 elderly controls. The DAT group was subdivided into different severity levels of dementia based on scores from the Mini-Mental State Exam: very mild (greater than or equal to 24), mild (20 to 23), moderate (10 to 19), and severe (0 to 9). The mean scores on the ADAS Cognitive subscale for the four levels of dementia (very mild = 23.1 +/- 7.7, mild = 22.9 +/- 8.9, moderate = 38.6 +/- 9.8, severe = 54.8 +/- 7.6) were statistically different from one another (p less than 0.0001, except very mild vs. mild) and were significantly worse than the scores of the elderly control group (5.5 +/- 2.7, p less than 0.0001, ANOVA). Furthermore, the ADAS Cognitive subscale was highly effective in discriminating individual Alzheimer patients from elderly controls. The ADAS Cognitive score correctly classified 100% of the very mild group, 91% of the entire mild group, and 100% of the moderate and severe groups when a cutoff score of 2 SDs above the control group mean was used. Age and education had only minimal effects on the ADAS Cognitive score. The ADAS is a valuable screening test that only takes 30 min to administer and has utility in both early detection and staging of DAT.

Adolescent↗
PubMed1992

Homoharringtonine is safe and effective for patients with acute myelogenous leukemia.

Homoharringtonine (HHT) is a cephalotaxine alkaloid with reported efficacy in acute myelogenous leukemia (AML). In a phase II trial, we evaluated HHT 5 mg/m2 by continuous infusion daily for 9 days in patients with relapsed or refractory acute leukemia and blastic phase of chronic myelogenous leukemia (BLCML). Sixty-six patients were entered. There were 40 males and 26 females with a median age of 41 years (range 15-81). Of 43 patients with relapsed AML, seven achieved a complete remission (16%, 95% confidence interval 5%-27%). Although 11 patients with AML primarily resistant to an anthracycline/cytarabine combination did not respond, two of three patients primarily resistant to low-dose cytarabine achieved complete remission. No patients with acute lymphoblastic leukemia, biphenotypic leukemia, or BLCML responded. Hypotension during the administration of HHT was the most difficult toxicity encountered, requiring multiple interruptions of therapy in several patients and the administration of intravenous saline. Fluid retention and weight gain occurred in 29% of patients. Transient asymptomatic hyperglycemia was observed in 63% of patients. Other toxicity was mild and included nausea and vomiting, diarrhea, mucositis, hepatic dysfunction, and cardiac arrhythmias. As expected, severe myelosuppression occurred in all patients. HHT is well tolerated, but with unique problems associated with administration. It has demonstrable efficacy in pre-treated patients with AML, but its role in the treatment of this disease remains to be defined.

Antineoplastic Agents, Phytogenic↗