Biomedical subjects
Publications and source records attributed to S Simon.
A total of 29 children and adolescents underwent surgery for cystic (n = 2) or pseudocystic (n = 23) lesions or papillary-cystic neoplasms (n = 2) of the pancreas. The special conditions of paediatric patients (differential diagnosis, management and prognosis of posttraumatic, postnecrotic, inflammatory and malignant diseases) are discussed in the present literature.
Complete tumor resection is often impossible in disseminated stages of neuroblastoma. Therefore, the role of primary tumor resection in neuroblastoma patients of stage III and IV will be discussed here. Between 1972 and 1995, 66 neuroblastoma patients were operated in our department of pediatric surgery, 41 of whom were treated before 1989 and are the subject of retrospective study. Eight children belonged to stage III, 15 to stage IV and two to stage IV-S. Primary tumor resection was carried out in 19 of 25 patients with disseminated tumor stages. Total resection (RO) was achieved in three cases (16%). Microscopic tumor remains (R1) were present in four, with macroscopic remains in 12 cases. Three disseminated neuroblastomas received preoperative chemotherapeutic treatment, followed by a delayed complete operative tumor resection in two cases. Temporary tumor remission after an incomplete primary operation (R2) was achieved with adjuvant postoperative chemo- and radiotherapy in six of 12 patients. The mortality rate was high (stage III: n = 5/8, stage IV: n = 14/15, stage IV-S: n = 2/2). We recommend preoperative chemotherapy in cases of infiltrative tumor growth of stage III and generally in stage IV. This therapeutic regime improves the rate of complete tumor resection with less intraoperative complications.
PURPOSE: To present the effects of different radiotherapeutic treatments on the morphonuclear characteristics and growth of the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: We collected MXT tumor cells by means of fine-needle aspirations during various radiotherapeutic treatments and analyzed the morphological aspects of the cell nuclei by means of the digital cell image analysis of Feulgen-stained nuclei. In addition, we studied the morphonuclear aspects of cells from MXT tumors that had been radioresistant cell enriched. These radioresistant cell-enriched tumors involved MXT tumors that had survived one or two previous radiotherapies. The radiotherapy-induced effects on the morphonuclear characteristics were monitored by means of both monovariate (one-way variance) and multivariate (principal components and step-wise linear discriminant) analyses. RESULTS: The monovariate analyses showed that radiotherapy significantly influenced the values of the parameters relating to nuclear size (nuclear area--NA), the frequency of small dense chromatin clumps (short run length emphasis--SRL) in the nuclei, and the overall chromatin condensation level (local mean--LM). The global effect corresponded to a decrease in the overall chromatin condensation level in the radioresistant cell-enriched MXT tumors. This decrease occurred concomitantly with an increase in the frequency of the small dense chromatin clumps in the nuclei and a decrease in the nuclear area. The multivariate analyses showed that it was possible to quantitate the proportion of "radiosensitive-like" and "radioresistant-like" cell nuclei in the various MXT tumor types under study. CONCLUSIONS: The development of certain morphonuclear parameters, that is, the NA, the SRL, and the LM, could be proposed to predict the response of human tumors to radiotherapy as, indeed, could the quantitation of the proportion of radioresistant cells.
Antibody response in HCV infection may be variable and the variability of the serological response could be due to the differences in HCV strains. Since the distribution of hepatitis C virus genotype has been found to be geographically dependent, it is important to determine the distribution of HCV genotype in various countries with high prevalence of chronic non-A, non-B hepatitis. In this study, serum HCV RNA was examined in 53 patients suspected of chronic non-A, non-B hepatitis with an anti-HCV test as determined by currently available assay. HCV viremia was detected in 48 patients (90.6%). These patients had elevated serum ALT level at the time of HCV RNA determination. Using specific genotype probes, all isolates were classified into three different genotypes. Double and triple infections were also noted. HCV genotype 1b is the predominant genotype found in chronic hepatitis C patients in Jakarta.
27Al and 11B magic-angle spinning nuclear magnetic resonance (MAS NMR) results are reported on aluminium borates of composition Al2(1 - x)B2xO3 (0 < or = x < or = 0.7). It is shown that starting from liquid precursors with hexa-coordinated Al and tri- and tetra-coordinated B, porous aluminium borates are obtained containing high fractions of penta-coordinated Al. The presence of boron in the crystalline phases stabilizes penta-coordinated Al, existing already in their amorphous precursors, and at the same time distorts the surroundings of the hexa-coordinated Al. The reversible effect of air exposure on low-coordinated Al (Al4C, Al5C) and B (B3C) proved that at least these species are situated at the surfaces of the pores. The A9B2 phase still contains a small fraction of tetra-coordinated B. The 27Al and 11B MAS NMR spectra of A9B2 show a well-resolved powder spectrum with no indication of broadening due to a distorted configuration.
The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.
It is well known that patients requiring long-term mechanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative organisms. However, useful parameters to objectively describe the airway inflammation associated with airway instrumentation and colonization have not been well define. In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique population for studying airway inflammation and infection. To quantitate production of respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h period. Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%). With these techniques, patients were then studied serially over a 4- to 7-week period. Total cell count, inflammatory cell differential, and two indices of airway inflammation, human neutrophil elastase (HLE) and soluble-intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored. The mean total cell count was 42.2 x 10(6) cells per gram of secretions when patients were clinically stable and not receiving antibiotics. The average differential was neutrophils 69.9%, macrophages 26.9%, and lymphocytes 2.8%. Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was 83 ng/mL. Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of secretions was measured (p < 0.018). The total cell count and percent neutrophils decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%, respectively. While these changes were not statistically significant, the absolute number of airway neutrophils over the 6 h decreased sevenfold (p < 0.014). Similarly sICAM-1 burden (micrograms per 6-h period) also decreased significantly (p < 0.034). These patients provide a unique human model for future studies specifically designed to assess the effect of novel modalities of anti-inflammatory and antimicrobial agents on respiratory secretions.
We are in the process of establishing a pharmacokinetic database for drug dosage adjustment to impaired renal function. To meet these demands, the system needs a unifying pharmacokinetic concept. Drug clearance is the common parameter that allows for intersecting the different pharmacokinetic approaches. In addition, two parameters are essentially needed for the concept, either the area-derived volume and the dominant elimination half-life or the moment-derived volume and the mean residence time. For drugs where the area-derived volume decreases with renal impairment, it can be shown that compartment-derived parameters are explicitly convertible into moment-derived parameters and vice versa.
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Many anticancer drugs are classified as either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by transmembrane pH gradients. Indeed, development of multidrug resistance (MDR) in tumor cells has been correlated with an alkaline shift of cytosolic pH. To examine the role of pH in drug partitioning, the distribution of two drugs, doxorubicin and daunomycin, was monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly accumulated within the cells. The highest concentrations were measured in the most acidic compartments--e.g., lysosomes. Modifying the cellular pH in drug-sensitive cells to mimic reported shifts in MDR caused an immediate change in the cellular drug concentration. Drug accumulation was enhanced by acidic shifts and reversed by alkaline shifts. All of these effects were rapid and reversible. These results demonstrate that the alkaline shift observed in MDR is sufficient to prevent the accumulation of chemotherapeutic drugs independent of active drug efflux.
To elicit antibodies directed specifically against the neuron-specific form of the c-src gene product, pp60c-src(+), we used an antigenized antibody comprising a decamer containing the amino acid sequence specific to pp60c-src(+) inserted into the third hypervariable loop of the heavy (H)-chain variable (V)-region. This was used to raise anti-idiotype antibodies reacting with the peptide epitope in rabbits. The antisera reacted with pp60c-src(+), as judged by immune blotting, immunoprecipitation, immune complex kinase assay, and indirect immunofluorescence staining, but did not react with the fibroblast form of the c-src gene product, pp60c-src. Antigenized antibody is a useful approach for producing antibodies able to distinguish between isoforms of the same gene product and specific for the neuronal form of the Src protein.
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The functional characteristics of neutrophils are exceedingly sensitive to physiological conditions as well as the details of isolation. Exposure to lipopolysaccharide (LPS) or even contamination of the isolating media with traces of LPS is known to play an important role in regulating cell function and expression of receptors. Because of the suspected role of CD14 as a receptor for LPS, we used anti-CD14 monoclonal antibodies both to identify CD14 in the cell surface of polymorphonuclear leukocytes and to inhibit functional changes elicited by LPS. Cytometric techniques were used to investigate the regulation of CD14 and CR3 on the neutrophil cell surface in whole blood to minimize any effects of isolation. In whole blood neutrophil express low levels of formyl peptide receptor, CD14, and CR3, which increase substantially in response to formyl peptide and LPS. The increases in CR3 and CD14 occurred in parallel and were independent of protein synthesis and tumor necrosis factor (TNF) production. The increase in CR3 was inhibited by antibodies MY4, 3C10, and 28C5 against CD14. These findings are consistent with the notion that in blood the observed receptor up-regulation is in direct response to the action of LPS on neutrophils through CD14 and does not require products from macrophages such as TNF or the production of C5a from the plasma.
The acute-phase reactant serum amyloid A (SAA) is a polymorphic apolipoprotein encoded by a family of highly homologous and closely linked genes: SAA1, SAA2, and SAA3. We have isolated a human genomic cosmid clone containing the gene encoding a fourth, constitutively expressed member of the human SAA superfamily, C-SAA, together with an SAA2*2 (SAA2 beta) gene. The gene encoding C-SAA shares the same 5' to 3' orientation as SAA2*2 and has the characteristic four-exon structure of the other members of the SAA superfamily. The exons of the gene encoding C-SAA share only limited sequence identity with those of SAA1, SAA2, and SAA3; they specify an mRNA, represented by the CS-1 cDNA reported previously by us, which is expressed at low levels (relative to the acute-phase SAAs) in normal and acute-phase liver. The gene encoding C-SAA is located 9 kb downstream of SAA2*2 and therefore occupies the locus that has been identified as containing the SAA4 gene.
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The French law on organ harvesting in brain dead patients allows this to be done without the family's consent, but prescribes to inform the relatives. Despite this, most teams do not harvest organs if the family is strongly opposed to the procedure. Information given to the relatives is therefore a very important point in the management of the donor. This prospective multicentre enquiry was designed to assess the conditions in which relatives were informed, and to determine the criteria which improve the rate of consent for the donation. After such information had been given, a questionnaire was filled in and sent to France-Transplant. Two hundred and seven interviews were analysed over an 18-month period. In two thirds of cases, the relatives were interviewed less than three hours after the diagnosis of brain death had been made. A written information sheet was used in only one third of interviews. Information was given by telephone in 11% of cases. Organ donation was accepted, on average, in 74% of cases. This ratio, which did not depend on the hospital, increased with the age of the donor: 66% for donors aged less than 18 years to 86% for those more than 50 years old. The aetiology of brain death was not a factor determining acceptance of the donation. The main factor was the conditions of interview: acceptance rate was the highest when there was a one hour delay between giving the information on the donor's brain death and that concerning organ donation.(ABSTRACT TRUNCATED AT 250 WORDS)
A conceptual model for studying the involvement of the central nervous system (CNS) in the performance of lateral swaying movements is described. The model is based on a four-link planar biped that approximates gross human locomotion in the frontal plane. The viscoelastic function of the musculoskeletal system provides a linear controller for the system. Such an intrinsic controller can effectively duplicate simple well-learned tasks in the absence of higher level CNS feedback. This hypothesis is supported by comparing the proposed controller with two neurophysiologically involved linear decoupling schemes. Reference trajectories for swaying commands are recorded from experiments conducted in the Gait Analysis Laboratory of the Ohio State University Hospitals. These reference trajectories are inputs to all three controllers. The viability of intrinsic feedback scheme in the execution of swaying tasks is demonstrated via comparison of responses from the three controllers.
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