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Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 127 records · Page 7Linked to original sources

Challenge of Goodness II: new humanitarian technology, developed in croatia and bosnia and Herzegovina in 1991-1995, and applied and evaluated in Kosovo 1999.

This paper presents improvements of the humanitarian proposals of the Challenge of Goodness project published earlier (1). In 1999 Kosovo crisis, these proposals were checked in practice. The priority was again on the practical intervention - helping people directly - to prevent, stop, and ease suffering. Kosovo experience also prompted us to modify the concept of the Challenge of Goodness. It should include research and education (1. redefinition of health, 2. confronting genocide, 3. university studies and education, and 4. collecting experience); evaluation (1. Red Cross forum, 2. organization and technology assessment, 3. Open Hand - Experience of Good People); activities in different stages of war or conflict in: 1. prevention (right to a home, Hate Watch, early warning), 2. duration (refugee camps, prisoners-of-war camps, global hospital, minorities), 3. end of conflict (planned, organized, and evaluated protection), 4. post conflict (remaini ng and abandoned populations, prisoners of war and missing persons, civilian participation, return, and renewal). Effectiveness of humanitarian intervention may be performed by politicians, soldiers, humanitarian workers, and volunteers, but the responsibility lies on science. Science must objectively collect data, develop hypotheses, check them in practice, allow education, and be the force of good, upon which everybody can rely. Never since the World War II has anybody in Europe suffered in war and conflict so much as peoples in Croatia, Bosnia and Herzegovina, and Kosovo. We should search for the meaning of their suffering, and develop new knowledge and technology of peace.

Altruism↗

Paclitaxel and UFT plus oral calcium folinate in pretreated metastatic breast cancer.

This phase I study was designed to determine the maximum tolerated dose (MTD) and dose-limiting side effects of combination treatment with paclitaxel (Taxol) and UFT (uracil and tegafur in a 4:1 molar ratio) plus oral calcium folinate (Orzel) for advanced metastatic breast cancer. After premedication, patients received paclitaxel as a 3-hour IV infusion (175 mg/m2) on day 1; UFT was administered orally at 300 mg/day (dose level 1), 400 mg/day (dose level 2), 500 mg/day (dose level 3), or 600 mg/day (dose level 4) in combination with 90 mg/day of calcium folinate in three divided doses for 14 days. Twenty patients with pretreated metastatic breast cancer have entered the trial so far. The main toxicity was neutropenia, occurring in 68% of patients. World Health Organization grades 1 and 2 peripheral neuropathy, arthralgia, and myalgia were common but not dose-limiting. All patients had grade 3 alopecia due to paclitaxel. One of six patients treated at dose level 4 experienced a dose-limiting toxicity with neutropenic fever. But within four dose levels MTD was not reached, and the study will continue to accrue patients to dose level 5. Objective responses were observed at all dose levels. In conclusion, the combination of paclitaxel and UFT plus oral calcium folinate seems to be a convenient and effective regimen for patients with pretreated metastatic breast cancer. Phase I is ongoing in order to determine MTD and the recommended dose for phase II testing.

Administration, Oral↗

Influence of radiation synovectomy on articular cartilage, synovial thickness and enhancement as evidenced by MRI in patients with chronic synovitis.

UNLABELLED: Radiation synovectomy is a safe and effective treatment for chronic synovitis that is refractory to the repetitive, intra-articular application of glucocorticosteroids in patients with rheumatoid or seronegative arthritis. Short-term and long-term effects of radiation synovectomy on articular cartilage, synovial enhancement and thickness were assessed in a prospective, clinical trial by MRI. METHODS: Thirteen patients (mean age 39+/-13 y) were treated with a median activity of 8.4 GBq 165Dy ferric hydroxide, a radionuclide with favorable physical properties and a well-documented clinical safety and efficacy profile. MRI was performed on a 1.5-T MR unit using a circular polarized knee coil. RESULTS: After a mean observation period of 13 mo, a marked reduction in synovial enhancement was observed in 10 patients. The mean reduction in baseline synovial thickness (mean 7.6+/-3.0 mm) was 24% (P = 0.03) at 1 wk and 42% (P = 0.01) about 1 y after treatment, respectively. Clinically, 9 of 13 patients (69%) exhibited persistent response to radiation synovectomy. The local clinical score, as defined by the reduction in pain, pannus, joint effusion and by the increase in the range of motion, improved significantly (P = 0.01), from a median of 7 (range 4-10) to a median of 2 (range 0-9). One year after treatment, changes in the local clinical score were related to the decrease in synovial enhancement in MRI (r = 0.7, P = 0.008, n = 12). There were no persistent adverse effects, nor was there evidence for any severe radiation-induced damage to the articular cartilage. On later follow-up images, the structure of the articular cartilage remained unaltered in all but 3 patients, who had new, superficial erosions most likely attributed to an active disease with persistence of inflammation. CONCLUSION: This study suggests that radiation synovectomy with 165Dy-ferric hydroxide is effective in terms of reducing chronic synovitis without causing detectable harm to the articular cartilage, as shown by MRI.

Adult↗

Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma.

Limb salvage surgery in patients with osteosarcoma is reported to cause a higher rate of local recurrences with a poorer chance of survival. It was the aim of the study to analyze differences between ablative and limb sparing surgery in patients with osteosarcoma who are treated with chemotherapy with respect to local and systemic tumor control and to determine independent prognostic factors. One hundred thirty consecutive patients younger than the age of 21 years who were operated on at the authors' institution for osteosarcoma of the extremities were reviewed. Histologic evaluations of surgical margins according to Enneking and coworkers revealed mostly wide (n = 109) and radical (n = 10) resection margins. The 5-year disease free survival rate was 60% for those patients treated by amputation and 71% for those treated by limb salvage. The overall local recurrence rate was 2.3%; 4.3% for ablation but only 1.2% for limb sparing surgeries. Multivariate analysis showed an independent effect of tumor volume, response to chemotherapy, and as expected, metastases at the time of diagnosis on overall survival. These data indicate that in patients where wide or radical tumor resection can be achieved, no difference in the outcome between ablative and limb sparing surgery occurred in local and systemic tumor control.

Adolescent↗

Absence of B7.1-CD28/CTLA-4-mediated co-stimulation in human NK cells.

Recent studies have suggested that B7-CD28 interactions provide co-stimulatory signals for activation of NK cells. Transduction of the B7.1 (CD80) gene into tumor cells has been shown to trigger proliferation and cytotoxicity of murine NK cells and a human NK cell line, YT2C2. Therefore, transduction of the B7.1 gene into CD80-negative human squamous cell carcinomas of the head and neck (SCCHN) and its stable expression was expected to upregulate proliferation and cytotoxic activities of human NK cells. However, expression of the B7.1 receptors, CD28 and CTLA-4, could not be demonstrated on the surface or in the cytoplasm of normal human NK cells, irrespective of the state of their activation. In proliferation experiments or various cytotoxicity assays, utilizing highly purified human NK cells as responder or effector cells, no enhancement of NK cell generation or activity, respectively, by B7.1+ SCCHN was observed relative to non-transduced or LacZ gene-transduced SCCHN. In contrast, co-incubation of B7.1+ SCCHN targets with human NK cells induced significant inhibition of NK cell growth. Thus, the B7.1-CD28/CTLA-4 pathway is not involved in triggering of human adult NK cells.

Abatacept↗

[Special diagnostic problems in primary malignant bone tumors].

The diagnosis of primary malignant bone tumors, which only account for 1% of malignancies in humans, represents quite a challenge for the pathologist. Apart from the often overlapping morphology between different entities, heterogeneity within one and the same tumor has to be kept in mind. Furthermore, in most cases the diagnosis must be established based on small biopsy specimens and occasionally even on frozen sections. In this context detailed clinical information including the patient's age and exact localization of the tumor, as depicted by X-ray or MRI, are essential requirements for a correct diagnosis. In addition, multiple biopsies from different tumor sites may be of help. For example, 25% of osteogenic sarcomas (OSA) are chondroplastic. Others may contain areas similar to fibrosarcoma (FSA) or malignant fibrous histiocytoma (MFH). Since 90% of OSA occur in the second decade of life whereas chondrosarcomas, FSA and MFH usually manifest after the age of 40 years, a biopsy solely composed of malignant chondromatous tissue obtained from a tibial lesion of a 10-year-old child should most likely be considered as part of an OSA. In the differential diagnosis of the so-called small, round cell tumors, which include Ewing sarcoma, malignant lymphoma and small-cell OSA, immunohistochemical staining of the paraffin-embedded material and a molecular biological/genetic work-up of frozen material are most helpful. In this paper the histomorphological characteristics and criteria for differential diagnosis of the most common primary malignant bone tumors are discussed.

Bone Neoplasms↗

[Primary malignant bone tumors. Clinical aspects and therapy. Vienna Bone Tumor Registry].

Diagnosis, concepts of therapy and prognosis of primary malignant bone tumors require intensive cooperation between orthopedic surgeons, radiologists and pathologists with special knowledge in oncology. The present paper demonstrates relevant topics of diagnosis, radiological appearance and therapy of the osteosarcoma, Ewing's sarcoma, chondrosarcoma and malignant fibrous histiocytoma based on the material of the Vienna Bone Tumor Registry and more than 35 years of cooperation between the Institute of Pathology and Anatomy and the Department of Orthopedics at the University of Vienna.

Bone Neoplasms↗

Production and structure elucidation of di- and oligosaccharide lipids (biosurfactants) from Tsukamurella sp. nov.

The bacterium Tsukamurella sp. nov., isolated from soil, was found to produce novel glycolipids when grown on sunflower oil as the sole carbon source. The glycolipids were isolated by chromatography on silica columns and their structures elucidated using a combination of multidimensional NMR and MS techniques. The three main components are 2,3-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D-glucopyranose, 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-4,6-di-O-acyl-alpha-D- glucopyranosyl-(1-1)-alpha-D-glucopyranose and 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-beta-D-galactopyranosyl- (1-6)-4,6-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D- glucopyranosyl which are linked to fatty acids varying in chain length from C4 to C18. The glycolipids are mainly extracellular but are also found attached to the cell walls. During the cultivation the composition of the glycolipids changed from disaccharide- to tri- and tetrasaccharide lipids. The glycolipids show good surface-active behaviour and have antimicrobial properties.

Actinomycetales↗

Cardiac operations in patients with cirrhosis.

BACKGROUND: A retrospective review was performed to determine the outcome after cardiac operations in patients with a documented history of noncardiac cirrhosis. METHODS: The charts of patients admitted to the cardiothoracic surgical service between 1990 and 1996 were reviewed, and 13 patients with a preoperative history of cirrhosis were identified. The severity of preoperative liver disease was graded according to the criteria of Child. RESULTS: Most of the cases of cirrhosis were alcohol-related. Eight patients were classified as having Child class A and 5 as having Child class B cirrhosis. One hundred percent of patients with Child class B and 25% of those with Child class A cirrhosis had major complications. The postoperative chest tube output and transfusion requirements of these patients were approximately three times higher than average. The overall perioperative mortality rate was 31%. In patients with Child class B cirrhosis, the mortality rate was 80%. No patient with Child class A cirrhosis died. Deaths were related to gastrointestinal and septic complications, and not to cardiovascular failure. CONCLUSIONS: These findings suggest that patients with minimal clinical evidence of cirrhosis can tolerate cardiopulmonary bypass and cardiac surgical procedures, whereas those with more advanced liver disease should not be offered operation.

Aged↗

Comprehensive multimodality blood conservation: 100 consecutive CABG operations without transfusion.

BACKGROUND: Despite the recent introduction of a number of technical and pharmacologic blood conservation measures, bleeding and allogeneic transfusion remain persistent problems in open heart surgical procedures. We hypothesized that a comprehensive multimodality blood conservation program applied algorithmically on the basis of bleeding and transfusion risk would provide a maximum, cost-effective, and safe reduction in postoperative bleeding and allogeneic blood transfusion. METHODS: One hundred consecutive patients undergoing coronary artery bypass grafting were prospectively enrolled in a risk factor-based multimodality blood conservation program (MMD group). To evaluate the relative efficacy and safety of this comprehensive approach, comparison was made with a similar group of 90 patients undergoing coronary artery bypass grafting to whom the multimodality blood conservation program was not applied but in whom an identical set of transfusion guidelines was enforced (control group). To evaluate the cost effectiveness of the multimodality program, comparison was also made between patients in the MMD group and a consecutive series of contemporaneous, diagnostic-related group-matched patients. RESULTS: One hundred consecutive patients in the MMD group underwent coronary artery bypass grafting without allogeneic transfusion. This compared favorably with the control population in whom a mean of 2.2 +/- 6.7 units of allogeneic blood was transfused per patient (34 patients [38%] received transfusion). In addition, the volume of postoperative blood loss at 12 hours in the control group was almost double that of the MMD group (660 +/- 270 mL versus 370 +/- 180 mL [p < 0.001]). Total costs for the MMD group in each of the three major diagnostic-related groups were equivalent to or significantly less than those in the consecutive series of diagnostic-related group-matched patients. CONCLUSIONS: Comprehensive risk factor-based application of multiple blood conservation measures in an optimized, integrated, and algorithmic manner can significantly decrease bleeding and need of allogeneic transfusion in coronary artery bypass grafting in a safe and cost-effective manner.

Algorithms↗

Evidence for the involvement of the hydroxyl radical in the pathogenesis of excessive connective tissue proliferation in patients with tumor-endoprostheses.

Extensive proliferation of connective tissue around Vitallium implants can be observed in young patients who had limb salvage for primary malignant bone tumors. The underlying mechanism of excess proliferation and collagen accumulation is not known. We were therefore interested to show whether the alloy of the implant induced proliferation of fibroblasts in vitro, acted by a cytotoxic mechanism or generated free radical cross linking of collagen with subsequent accumulation. In vitro tests for proliferation and cytotoxicity using the implant material which consists of a series of transition metals, ruled out a proliferation-inducing or cytotoxic effect of the implant. Determination of ortho-tyrosine (OT), a marker for hydroxyl radical attack on phenylalanine, in the proliferating tissues surrounding the implants revealed significantly higher aromatic hydroxylation in the vitallium surrounding tissue correlating with tissue collagen content (r = 0.86, p < 0.01). Based upon the findings of increased OT and the presence of higher molecular weight bands on SDS-PAGE, representing more cross linked collagen, we suggest that hydroxyl radical attack lead to free radical mediated cross linking of collagen with subsequent collagen accumulation, as collagen cross-linked to a higher degree is less susceptible to proteolytic degradation.The hydroxyl radical attack seems to having been generated by the many transitional metals of the vitallium-alloy.

Adolescent↗

Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy.

Although the therapeutic outcome of osteosarcoma patients has improved dramatically within the last 20 years because of combined neoadjuvant chemotherapy and surgery, the problem of drug resistance remains. Thus far, markers that can predict the response to chemotherapy at the time of biopsy are not available. Heat shock proteins (hsp) 60, 72, and 73 have been shown to play a role in tumor immunity, and our study investigated their expression in human osteosarcomas and nonmalignant bone tumors before neoadjuvant chemotherapy. Immunohistochemical evaluations of hsp expression was performed on paraffin-embedded sections of 45 patients (17 female, 28 male, aged 6.5 to 62 years; mean, 19.4 years) with high-grade osteosarcoma at the time of biopsy, before preoperative chemotherapy. These results were correlated to histological response to chemotherapy, tumor size, age, alkaline phosphatase serum levels, and duration of symptoms. Thirty-four patients (15 male, 19 female, mean age 27 years) with osteoblastoma, osteoid-osteoma, or fibrous dysplasia served as nonmalignant controls. Hsp60 was uniformly found in the cytoplasm of both benign and malignant bone tumors. Nuclear hsp73 expression quantitatively increased in osteosarcoma cells. Hsp72 was significantly overexpressed in osteosarcomas (17 of 45, 38%) compared with nonmalignant bone tumors (1 of 34, 2.9%; P < .001). Hsp72-positive osteosarcomas responded better to neoadjuvant chemotherapy than hsp72-negative cases (P < .001), co-express hsp60, and correlate with higher tumor size (P < .005) and location in the distal femur. No differences were observed relative to age, gender, duration of symptoms, alkaline phosphatase levels, or hsp73 expression between hsp72-positive and hsp72-negative tumors. Hsp72 expression seemed to be a predictive immunohistochemical marker for osteosarcoma, because it is the first marker to prospectively correlate to response to neoadjuvant chemotherapy. It therefore, may be of importance in preoperative therapy regimens for nonresponding high-risk patients.

Adolescent↗

Permeation and pathways of human calcitonin (hCT) across excised bovine nasal mucosa.

In vitro permeation of human calcitonin (hCT), salmon calcitonin (sCT), and the somatostatin analog octreotide (SMS) through excised bovine nasal mucosa was studied applying donor/receiver experiments and confocal laser scanning microscopy. Permeabilities of gonadorelin, buserelin, Hoe013, and of thymopoietin fragments TP5 and TP4 were also included. Apparent permeability coefficients (Peff) ranged between 4 x 10(-5) (SMS) and 1.7 x 10(-5) cm s(-1) (TP4). Such Peff are typical for leaky-type airway epithelia. The order of permeabilities was: SMS >> hCT, sCT > buserelin, Hoe013 >> TP5 > TP4, LHRH. The relatively high permeability of hCT and sCT contrasted to their high molecular weight. At 37 degrees C, the permeability of hCT from mucosal to serosal (m-to-s) was found two-fold higher (p < 0.05) than from serosal to mucosal (s-to-m). Controls using 3H-mannitol showed equal permeabilities in both directions. At 4 degrees C, permeation of hCT was reduced but equal in both directions (m-to-s and s-to-m). As evaluated by confocal laser scanning microscopy, uptake studies with FITC-18-hCT revealed intracellular fluorescence in the epithelial cells, at 10 min/10 microM exposure in the form of fluorescent vesicles. By combination of these findings, an endocytotic pathway is suggested to contribute to the transport of hCT through nasal epithelium.

Animals↗

Evaluation of HLA-DR expression and T-lymphocyte infiltration in osteosarcoma.

Although in recent years the outcome of patients with osteosarcoma has considerably been improved by combining neoadjuvant chemotherapy with radical surgery, there still remains the problem of nonresponse to chemotherapy. T-lymphocytes play a critical role in tumor immunology, and MHC molecules are of central importance in the regulation of the immune response. It is the aim of this study to investigate whether T-lymphocyte infiltration of osteosarcomas and HLA-DR expression on tumor cells and infiltrating immune cells are of predictive or diagnostic value. Expression of CD3, CD8 and HLA-II was evaluated immunohistochemically on paraffin-embedded sections of 35 patients with high-grade osteosarcoma at the time of biopsy before chemotherapy and correlated with histologic response to chemotherapy, tumor size, age, alkaline-phosphatase serum levels and duration of symptoms. Thirty-four patients with osteoblastoma (n = 7), osteoid osteoma (n = 7) or fibrous dysplasia (n = 20) served as controls. Osteosarcomas were infiltrated by CD3+ (33/35, 95%) and CD8+ T-lymphocytes (24/35, 68%), non malignant bone tumors by CD3+ in 91% (31/34) and CD8+ T-lymphocytes in 74% (25/34), respectively. T-lymphocytes were positive for HLA-DR expression in 29% (10/35) in osteosarcomas and in 11% (4/34) in non-malignant controls. Osteosarcoma cells were positive for HLA-DR in 11/35 (31%) and non-malignant tumor cells in only 9% (3/34). Therefore, HLA-DR is overexpressed in osteosarcoma (p < 0.05). HLA-DR expression on osteosarcoma cells showed a positive correlation with HLA-DR expression on lymphocytes (p < 0.001) as well as with duration of symptoms and age (p < 0.05). Response to preoperative chemotherapy, gender, tumor size and serum alkaline-phosphatase levels did not correlate with the expression of the molecules tested. Our results show that HLA-DR is overexpressed in osteosarcoma cells compared to non-malignant bone-tumors. This overexpression, however, fails to serve as a predictive marker for response to neoadjuvant chemotherapy. The same is also true for tumor-infiltrating lymphocytes expressing CD3, CD8 and HLA-DR. Increased HLA-DR expression in osteosarcoma is most likely due to the immune response against the tumor.

Adolescent↗

A case of aneurysmal bone cyst in father and son.

The authors report a familial case of primary aneurysmal bone cyst in father and son, affecting both at the same location at nearly the same age. This fact again raises the speculation of a genetic link as another factor in the pathogenesis of aneurysmal bone cyst.

Adolescent↗