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Biomedical subjects

S Simon

Publications and source records attributed to S Simon.

At least 73 records · Page 4Linked to original sources
PubMed1997

Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591.

BACKGROUND & AIMS: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC. METHODS: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration. RESULTS: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10). CONCLUSIONS: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.

Adolescent↗
PubMed1997

alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.

The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Adult↗
PubMed1997

Detection of phosphatidylinositol glycan class A gene transcripts by RT in situ PCR hybridization. A comparative study using fluorescein, Texas Red, and digoxigenin-11 dUTP for color detection.

Gene-specific probes labeled with fluorescein, Texas Red, and digoxigenin-11 dUTP (DIG) were used for RT in situ PCR hybridization to detect PIG-A gene (phosphatidylinositol glycan class A) transcripts. The PIG-A gene is responsible for biosynthesis of the glycosylphosphatidyl-inositol (GPI) anchor. Lack of GPI anchor expression due to mutations can cause an acquired clonal hematologic disorder called paroxysmal nocturnal hemoglobinuria (PNH). In this RT in situ PCR study, two types of labeling methods, a direct method (using fluorescein and Texas Red) and an indirect method (using DIG-11 dUTP) were compared. Both were successfully applied to detect and localize the PIG-A gene transcripts within single cells of the cell lines AA2, H9, and JY. Furthermore, similar results for sensitivity and reproducibility were obtained. Advantages and disadvantages of the different labeling techniques are discussed. In addition, peripheral blood mononuclear cells from PNH patients were also included in this study.

Cells, Cultured↗
PubMed1997

The effect of fatigue on multijoint kinematics, coordination, and postural stability during a repetitive lifting test.

Because of the inability of strength tests to accurately discriminate between low back pain patients and healthy subjects, a multifactorial evaluation of low back pain patients is warranted. It is postulated that measurements of endurance, kinematics, postural stability, and coordination, in addition to strength, are necessary to fully document the patients' functional capabilities. This research study was conducted in order to understand the effects of fatigue on the above factors. Twelve healthy male subjects performed a repetitive lifting test in which a submaximal load was lifted at a maximal rate. Knee, hip, and trunk motion was measured using videography and electrogoniometry, postural stability was measured using a forceplate, and coordination parameters were determined using phase-plane analysis. Fatigue was documented by a 31% reduction in lifting power. At the end of the endurance test, there was less knee and hip range of motion and greater spine peak flexion, while the coordination measures demonstrated that there was greater hip and lumbar spine extension earlier in the lifting phase. The postural stability declined as the test endured. Utilization of these measures may guide physical therapists in their rehabilitation of low back pain patients.

Adult↗
PubMed1997

Neuromuscular trunk performance and spinal loading during a fatiguing isometric trunk extension with varying torque requirements.

A novel testing protocol was used to investigate changes in neuromuscular performance, muscle recruitment, and spinal loading as subjects became fatigued while performing an isometric endurance test of varying torque requirements. There was decreased accuracy in maintenance of a reference torque but no change in response time as subjects became fatigued. The study of trunk-muscle recruitment indicated significant increases in internal oblique and latissimus dorsi muscle activity. This change in recruitment led to changes in spinal loading despite a relatively constant torque output. The use of an electromyogram (EMG)-assisted model demonstrated that when subjects are expected to become fatigued during test performance, the assumption of a constant maximal stress capacity of the muscle may not be robust.

Adult↗
PubMed1996

License plate confiscation for persistent alcohol impaired drivers.

Minnesota cancels the registrations and confiscates the license plates of vehicles driven by repeat drinking drivers in a procedure which prior research has demonstrated to be effective in reducing subsequent recidivism. The research reported here concerns the problems experienced in the functioning of this law. Samples of officials and repeat driving under the influence (DUI) offenders were interviewed in Minnesota and in the neighboring state of Iowa, chosen for comparison because its laws also provide for plate confiscation, but using a judicial rather than an administrative procedure. In addition, representative samples of the driving and vehicle registration records of convicted drunk drivers and of routine traffic offenders were analyzed. The research found that evasion of plate impoundment orders by drivers, though apparently easy to accomplish, appeared to be rare. However, the orders were themselves not issued in a large proportion of cases where they were prescribed by statute, potentially weakening the effectiveness of the law. The reasons, with possible countermeasures, are explored in this report.

Adaptation, Psychological↗
PubMed1996

Safety concerns affecting delivery of home health care.

Factors influencing the remarkable growth of home health care include increased elderly population, decreased average length of hospital stay, and technological advancements that reduce the need for hospitalization. Societal changes have prompted increasing concern about personal risk to home care providers. The purpose of this pilot study was to: 1) ascertain factors related to perception of risk by home health care administrators and staff and to identify strategies used by home health care administrators to reduce risk to staff; and 2) determine whether quality of care is affected when home-visit situations present risk. A convenience sample of 36 home health care administrators and 62 staff was surveyed about risks and measures provided by the home health care agency to minimize risk. Factors associated with risk are geographic location, high incidence of crime, inappropriate patient or caregiver behavior, infectious diseases, and evening assignments. Strategies used to minimize risk include safety programs, preplanning of visits, personal protective equipment, escorts, and buddy systems. Perceived ability to refuse high-risk assignments, however, is questionable, as 66% of the staff stated that they leave a situation "as soon as possible." These findings will be used to strengthen inservice programs and to provide a basis for future studies.

Adult↗
PubMed1996

Statistical analysis of heterogeneous pharmacokinetic data from the literature.

To obtain the reliable pharmacokinetic quantities necessary for the adjustment of individual drug dosages, the pharmacokinetic data in the literature must be analysed by various appropriate statistical methods. Generally, pharmacokinetic quantities have been calculated from small sample sizes and published in different ways (the coefficient of variation of an estimated pharmacokinetic quantity is often higher than 40 percent). In the present study data were therefore structured and clustered according to the important influence variables. The important influence variables were obtained by known multivariate statistical methods. To obtain optimal estimators (uniformly minimum variance unbiased estimators) for the quantities inside the clusters, goodness of fit tests must be performed. Skewed distributions and samples with heterogeneous variances must be subjected to transformation procedures to obtain normally distributed values with homogeneous variances. The population-derived estimate of the a priori knowledge of pharmacokinetic quantities can be obtained by a statistical algorithm proposed in this paper. Information on the quantities half-life, total body clearance and volume of distribution of vancomycin were extracted from over 200 publications. These data were analysed with the proposed statistical algorithm, yielding population-based estimates for half-life, clearance and volume of vancomycin, taking into consideration the detected influence variables--renal function and the age of the patient. Important dependencies between different variables are discussed.

Age Factors↗
PubMed1996

[Cyst, pseudocyst or carcinoma? Space-occupying lesions of the pancreas in childhood and adolescence].

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.

Abdominal Injuries↗
PubMed1996

["As much as possible"--an outdated concept in advanced neuroblastoma?].

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.

Adolescent↗
PubMed1995

Computer-assisted morphonuclear characterization of radiotherapy-induced effects in MXT mouse mammary adenocarcinomas surviving earlier radiotherapy.

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.

Adenocarcinoma↗
PubMed1995

Hepatitis C virus RNA detection and HCV genotype in patients with chronic non-A, non-B hepatitis in Jakarta.

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.

Adult↗
PubMed1995

High fraction of penta-coordinated aluminium in amorphous and crystalline aluminium borates.

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.

Aluminum Compounds↗
PubMed1995

Infantile osteopetrosis; bone marrow transplantation from a cousin donor.

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.

Bone Marrow Transplantation↗
PubMed1995

Tracheal aspirates in long-term mechanically ventilated patients. A human model of gram-negative infection and airway inflammation.

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.

Adult↗
PubMed1995

Unifying concept of pharmacokinetics derived from drug distribution and elimination in renal failure.

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.

Dosage Forms↗