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Biomedical subjects

D Beck

Publications and source records attributed to D Beck.

At least 19 recordsLinked to original sources
PubMed1996

Truly late onset of eating disorders: a study of 11 cases averaging 60 years of age at presentation.

OBJECTIVE: To study late-onset cases of eating disorders in order to (1) document the occurrence of these cases as truly new onset, even if postmenopausal; (2) to alert clinicians to the category of late-onset eating disorders, especially clinical features and treatment response; (3) to challenge some prevailing assumptions of etiology. METHODS: Selection of cases of eating disorders with first onset after age 40 that met DSM-IV criteria, by review of eating disorders admissions to three university hospital programs. RESULTS: Eleven patients, approximately 1% of all cases of eating disorders, had first onset of an eating disorder after age 40 and as late as 77, with an average onset of 56 and clinical presentation at 60 years. They met DSM-IV criteria for all subtypes of eating disorders. In general, concurrent medical and comorbid psychiatric symptoms made recognition and treatment more complex. DISCUSSION: Truly late-onset cases do occur, challenging etiological theories requiring adolescent age of onset, premenopausal endocrine functioning, or adolescent psychodynamic conflicts. Late-occurring cases, after accurate diagnosis, require an appreciation of psychological themes pertinent to this age group, such as bereavement or unresolved body image issues. Age by itself is no barrier to onset of eating disorders, which may occur whenever self-starvation and/or binge-purge behaviors become entrenched as sustaining behaviors for amelioration of psychodynamic conflicts, mood disorders, or interpersonal distress.

Age of Onset↗
PubMed1996

Ocular hemodynamic effects of acute ethanol ingestion.

PURPOSE: Because the protean biological effects of ethanol include acute alterations in both cortical function and circulatory control, we investigated the effect of acute alcohol consumption on retrobulbar hemodynamics and contrast sensitivity in healthy human volunteers. SUBJECTS AND METHODS: Twelve young adults received orange juice with and without ethanol in a double-masked fashion. The ethanol dose was sufficient to raise blood alcohol to 0.07 +/- 0.003 g/dl. Retrobulbar hemodynamics were assessed at baseline and twice at elevated blood alcohol by color Doppler imaging. RESULTS: Acute elevation of blood alcohol lowered intraocular pressure from 13.0 +/- 0.7 to 10.7 +/- 0.7 mm Hg (p < 0.05). In contrast, elevated blood alcohol left peak systolic velocity, end-diastolic velocity and the resistance index constant in three retrobulbar arteries (ophthalmic, central retinal and posterior ciliary). For example, in the central retinal artery, peak systolic velocity, end-diastolic velocity and the resistance index averaged 11.0 +/- 1.3 cm/s, 2.8 +/- 0.4 cm/s and 0.75 +/- 0.03 before ethanol, as compared with 10.5 +/- 1.0 cm/s, 2.9 +/- 0.3 cm/s and 0.72 +/- 0.03 after ethanol (all p = NS). Alcohol ingestion also failed to alter either visual acuity or contrast sensitivity, as assessed under both photopic and mesopic conditions. CONCLUSIONS: Although ethanol has widespread cognitive and cardiovascular effects, at blood levels near legal definitions of intoxication we found it ineffective in altering either retrobulbar hemodynamics or contrast sensitivity.

Adult↗
PubMed1996

Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.

PURPOSE: In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS: In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

Antibodies, Monoclonal↗
PubMed1995

Expression of stem cell factor and its receptor by human neuroblastoma cells and tumors.

Bone marrow (BM) is a frequent site of metastasis in children with neuroblastoma (NB). Nonhematopoietic cell lines of the same neuroectodermal origin produce both stem cell factor (SCF) and its receptor, the product of the c-kit protooncogene (c-kit). Because recombinant SCF is likely to be soon clinically tested to accelerate BM recovery after high-dose chemotherapy, a treatment administered to children with disseminated NB, we addressed the question of whether SCF/c-kit complex could play a role in the proliferation and metastasis of NB cells. Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lines and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by Western blotting in cell extracts or by surface immunofluorescence and flow cytometry. Soluble SCF protein was detected by enzyme immunoassay at low concentrations in the cell supernatants in the same 7 NB cell lines. Treatment of 4 NB cell lines by SCF +/- cytokines relevant to BM physiology did not induce c-kit antigenic expression or modulate 3H-thymidine uptake. Likewise, the latter was not changed by incubating the cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis showed weak diffuse or focal staining for SCF and c-kit in few primary or metastatic tumor samples, only once simultaneously. We conclude that NB cell lines usually produce low levels of soluble SCF but do not express c-kit and that both proteins are rarely detected in NB tumors. The SCF/c-kit complex appears to be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be safely administered to children with NB.

Cell Division↗
PubMed1995

Childhood NHL in Switzerland: incidence and survival of 120 study and 42 non-study patients.

Based on the Swiss Pediatric Oncology Group (SPOG) cancer registry data during 1981-1991, a high average incidence of 8 new NHL per million children younger than 15 years per year was found. Of 162 children with NHL registered in 1976-1991, 120 were study patients, i.e., officially registered and treated according to SPOG or Pediatric Oncology Group (POG) protocols, while 42 were non-study patients, i.e., patients not officially enrolled on protocols. Overall, 91 of 120 (76%) study patients remained alive. Seventy-nine study patients were treated according to older SPOG protocols, and 53 (67%) of these survived, while 38 of 41 (93%) study patients treated according to newer POG protocols remained alive (P = 0.0068). Only 22 (52%) of the 42 non-study patients survived (P = 0.0001). There was no improvement if the survival of non-study patients before and since 1986 was compared. Population-based treatment results in Switzerland were similar to those in the United Kingdom. They provided an important base for the development of future treatment strategies.

Adolescent↗
PubMed1995

Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer.

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.

Acute Disease↗
PubMed1995

Incidence of childhood acute lymphoblastic leukemia (ALL) and population-based treatment results in Switzerland: experiences with 507 study and 149 nonstudy patients.

Of 656 patients with ALL (all types) diagnosed in Switzerland during 4 consecutive 4-year periods (1976-1979, 1980-1983, 1984-1987, 1988-1991), 507 were officially registered on protocols ("study" patients) while 149 were not ("nonstudy" patients). The mean incidence of 3.8/100,000 children < 15 years/year is higher than reported for other Western countries. Evidence is presented suggesting that the 656 patients represent only approximately 90% of all children with ALL residing in Switzerland, indicating that the true incidence of ALL might even be higher. The fraction of "nonstudy" patients fell from 40% (1976-1979) to 15% (1984-1987). The rate of survival at 4 years of all patients with ALL ("study" and "nonstudy") increased by 17% during the three consecutive periods 1976-1979, 1980-1983, and 1984-1987. As expected, a higher increase (20%) was observed in "study" patients and a statistically nonsignificant lower one (10%) in "nonstudy" patients.

Adolescent↗
PubMed1995

Diagnosis and follow-up of neuroblastoma by means of iodine-123 metaiodobenzylguanidine scintigraphy and bone scan, and the influence of histology.

The purpose of this work was to compare technetium-99m-diphosphono-propanedicarboxylate (DPD) and iodine-123-metaiodobenzylguanidine (MIBG) scans in the diagnosis and follow-up of neuroblastoma, and to study the role of histological differentiation in the uptake of MIBG. The uptake of MIBG and of DPD were studied retrospectively in 27 patients with neuroblastoma (primary, residual and recurrent tumours as well as bone and bone marrow metastases). The findings were related to the histological classification of the tumours as neuroblastoma (N1), differentiating neuroblastoma (N2) or ganglioneuroblastoma (N3). Uptake of MIBG by the primary tumour occurred in 17 of 19 patients, either at diagnosis or during follow-up. There were only two false-negatives with MIBG, both of which were N3. Ten patients were studied preoperatively with both MIBG and DPD. The primary tumour showed MIBG uptake in nine of the ten and DPD uptake in eight of them. Thirty-five sites of cortical bone metastasis were shown in eight patients by both MIBG and DPD, 12 sites in seven patients by MIBG only and seven sites in five patients by DPD only. In 14 patients both MIBG and bone scan were negative. Overall, MIBG demonstrated more lesions than DPD. Retrospectively several hot spots seen only with the bone scan are to be considered as false-positive. The highest incidence of false-negative MIBG and bone scans was observed in ganglioneuroblastoma with a predominance of the more mature component (ganglioneuroma).

3-Iodobenzylguanidine↗
PubMed1995

Lysophosphatidylcholine-stimulated protein and glycoprotein production by human gallbladder mucosal cells.

It has been demonstrated in experimental cholecystitis in cats produced by lysophosphatidylcholine that the development of inflammation is associated with the exsorption of a large amount of protein into the gallbladder lumen. It was subsequently demonstrated that in feline experimental cholecystitis the protein produced was albumin and that its production was decreased by vesicular transport inhibitors, suggesting an active secretory process. In the present study, the effect of lysophosphatidylcholine on protein production by fresh, isolated human gallbladder mucosal cells was evaluated. Isolated gallbladder mucosal cells were incubated with [14C]leucine for 24 hr in tissue culture medium. The cells readily incorporated the radioactive label into cellular protein, a process inhibited by cycloheximide. Exposure of the cells to lysophosphatidylcholine for 1 hr in buffer solution resulted in loss of intracellular protein into the buffer solution. Exposure of the cells for 1 hr prior to lysophosphatidylcholine administration to vesicular transport inhibitors, colchicine, and cytochalasin B and to 4 degrees C culture conditions failed to alter the lysophosphatidylcholine-produced passage of the 14C label extracellularly. SDS-PAGE evaluation of the protein produced demonstrated that human gallbladder mucosal cells continuously produced a 66-kDa protein that was not increased by increasing concentration of lysophosphatidylcholine and a 14-kDa protein that increased with increasing concentrations of lysophosphatidylcholine. Employing Western blotting with specific antibodies, the 66-kDa protein was demonstrated to not be albumin but a 66-kDa glycoprotein, and the 14-kDa protein was demonstrated to contain phospholipase A2. Human gallbladder mucosal cells produced a protein and glycoprotein in response to lysophosphatidylcholine by a mechanism not related to vesicular transport.

Carbon Radioisotopes↗
PubMed1995

CD44 expression and modulation on human neuroblastoma tumours and cell lines.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment and tumour metastasis. A large family of variants or isoforms, generated by alternative splicing of a single gene, has been reported to be involved in the malignant process, by conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumour characterised by an aggressive and metastatic behaviour in advanced stages, with amplification of the MYCN protooncogene. In this report, we show that the CD44 standard molecule was highly expressed in the majority of tumours of stages 1-3, in all stage 4s and ganglioneuromas, but only in a subset of stage 4 tumours. A lack of CD44 expression was observed in all MYCN amplified stage 4 tumours, thus demonstrating a highly significant inverse relationship between MYCN amplification and CD44 expression in neuroblastoma. In addition, the expression of 4 different CD44 isoforms was measured on all specimens and was always found to be negative. Using neuroblastoma cell lines and MYCN expressing transfectants, we show that CD44 expression by neuroblastoma cell lines is not directly related to MYCN amplification, but is associated to the stage of differentiation or lineage, and to the tumorigenic properties of the cells. In addition, CD44 expression can be upmodulated parallel to differentiation or maturation as induced by retinoic acid, bromodeoxyuridine or phorbol ester. In contrast, cytokines such as IFN gamma, TNF alpha, or growth factors such as bFGF, SCF and TGF beta were ineffective in modulating CD44 expression.

Biomarkers, Tumor↗
PubMed1995

Effects of stem cell factor and other bone marrow-derived growth factors on the expression of adhesion molecules and proliferation of human neuroblastoma cells.

Metastasis in children with neuroblastoma (NB) is a poor prognostic factor despite intensive therapy. In the near future, stem cell factor (SCF) is likely to be used clinically to accelerate bone marrow (BM) recovery after high-dose chemotherapy in patients with advanced NB. The high frequency of BM metastases in NB could be secondary to BM-derived human growth factors (HGF) modulating the adhesion, secondary growth (or both) of circulating metastatic NB cells. To test this hypothesis, we studied the in vitro effects on NB cell lines grown in chemically defined medium of SCF, interleukin (IL)-1 beta, IL-3, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) used alone or in combination. The antigenic expression of NB-associated cell adhesion molecules (CAM) HLA class 1, intercellular CAM-1, neural-CAM and CD44 were assayed by monoclonal antibodies and flow cytometry, and DNA synthesis by 3H-thymidine uptake. The expression of CAM was not modulated by SCF or other HGFs. An increase in thymidine uptake was induced by bFGF alone in IMR-32 cells, while SCF and other HGFs had no notable effect. Our results indicate that SCF and other BM-derived HGFs are unlikely to have a generalised effect on the expression of adhesion molecules by NB cells or proliferation. The clinical administration of recombinant human SCF to children with NB should be safe.

Cell Adhesion Molecules↗
PubMed1995

Comparison of the flow rates of central venous catheters designed for rapid transfusion in infants and small children.

Large-bore Hickman catheters are useful in infants and small children for the rapid transfusion of blood or fluids into the central circulation. Recently high-flow plastic sheaths have been developed for the same purpose. We compared the flow rates of normal saline, 5% albumin and packed red blood cells through two sizes of Hickman catheters that have been recommended for major surgery in infants to five sizes of Arrow plastic sheaths of comparable external diameters, and to 14 and 16 gauge Jelco catheters. The flow rates of all three solutions through the plastic sheaths and the 14 gauge Jelco catheters were superior to both sizes of Hickman catheters. Shortening the Hickman catheters improved their flow. High-flow plastic sheaths can provide a useful alternative to Hickman catheters in patients where permanent, large-bore central venous catheters are not required. Hickman catheters should be shortened as much as safely possible if massive haemorrhage is anticipated.

Catheterization, Central Venous↗
PubMed1994

Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line.

We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.

Animals↗
PubMed1994

CD44H expression by human neuroblastoma cells: relation to MYCN amplification and lineage differentiation.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment, and tumor metastasis. Due to the alternative splicing of the single gene, a large family of different variants or isoforms is generated. Several reports have indicated an up-regulation of CD44 variant (v) isoforms in malignant process, conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor characterized by an aggressive and metastatic behavior in advanced stages with amplification of the MYCN protooncogene. In this report we show that the CD44 standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no expression of CD44 was detected on MYCN amplified stage IV tumors, thus demonstrating a highly significant negative relationship between MYCN amplification and CD44 expression in neuroblastoma. The expression of CD44 on neuroblastoma cultured cell lines was not shown to be related to MYCN amplification but rather linked to the S-type, schwann/glial differentiation lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6 antibodies and Northern blot analysis of mRNA from cell lines with probes spanning exons 4-10 did not reveal any expression of splice variants on neuroblastomas of all stages and cell lines, thus ruling out a major role of these isoforms in neuroblastoma progression and metastasis.

Blotting, Northern↗
PubMed1994

Treatment of relapsing acute lymphoblastic leukemia in childhood. III. Experiences with 54 first bone marrow, nine isolated testicular, and eight isolated central nervous system relapses observed 1985-1989.

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularly those with a bone marrow relapse while on therapy.

Adolescent↗
PubMed1994

Studies on the etiology of acute acalculous cholecystitis: the effect of lipopolysaccharide on human gallbladder mucosal cells.

Previous studies in animals have shown that lipopolysaccharide produces experimental cholecystitis possibly through a platelet-activating factor-prostanoid mediated process. In this study it was intended to evaluate the effect of LPS on primary cultures of human gallbladder mucosal cells. Gallbladder mucosal cells were isolated from gallbladders removed during routine cholecystectomies or other operations. The cells were cultured for 24 h before treatment. Unstimulated cells produced low levels of prostanoids and significant basal levels of PAF. LPS produced stimulation of eicosanoid and PAF secretion. The increased prostanoid formation was not enhanced when LPS and PAF were administered together. Prostanoid synthesis was inhibited by the administration of a cyclooxygenase inhibitor while administration of a PAF receptor antagonist significantly increased prostanoid formation, suggesting that increased PAF levels function as a negative control mechanism to decrease prostanoid synthesis. The results suggest that endotoxemia may produce a cascade of inflammatory processes in human gallbladder mucosal cells resulting in the development of acute acalculous cholecystitis.

Acute Disease↗
PubMed1994

[GRIN-endoscopy for laser treatment in ophthalmology].

Endoscopes for use in ophthalmology can be manufactured with diameters smaller than 0.89 mm. Because gradient-index (GRIN) lenses yield a higher resolution than ordered fiber bundles having the same diameter, GRIN lenses with a diameter of either 0.35 mm or 0.50 mm were utilized to manufacture thin high resolution endoscopes. Whatever the working distance, the resolution obtained with a GRIN lens having a diameter of 0.50 mm was higher than that obtained with a GRIN lens of 0.35 mm. Thanks to the miniaturization, an additional working channel could also be integrated within the endoscope. This allowed new combinations of various surgical instruments. This channel can be used as a guide for an optical fiber for laser therapy or as an irrigation/aspiration channel. The use of such an instrument where the observation path is parallel to the surgical instrument was compared to the application of the endoscope as a separate monitoring system. The advantages and inconveniences of both systems are discussed. Preference is given to a system where the diameter of the observation channel is maximum and the optical fiber for laser delivery is integrated but adjustable along its length within the endoscope.

Endoscopes↗