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Biomedical subjects

C J Kirkpatrick

Publications and source records attributed to C J Kirkpatrick.

170 records · Page 10Linked to original sources

In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum.

Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 micrograms/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage.

Cell Adhesion↗

Light- and electron-microscopic studies on multinucleated giant cells in sarcoid granuloma: new aspects of asteroid and Schaumann bodies.

Ultrastructural studies using transmission, analytical, electron, and light microscopy were performed on epithelioid granulomata in 4 lymph nodes from a case of sarcoidosis, emphasizing the organization of asteroid and Schaumann bodies in multinucleated giant cells and the deposition of chemical elements. Serial sectioning at semithin level showed a single multinucleated giant cell can contain up to 4 asteroid and 1 Schaumann body. Microtubules and centrioles were not found in asteroid bodies, although a centriolar field was present in 1 giant cell close to the plasma membrane, completely unrelated to the asteroid body. In 1 asteroid body, tubulelike structures were observed in a focus showing filament dissociation. A principal ultrastructural finding is intimate envelopment of radiating filamentous arms of the asteroid body by myelinoid membranes, extensive forms of which are also present between the arms. Elemental analysis revealed a definite peak of calcium and a probable phosphorus peak in relation to the asteroid body and associated myelinoid membranes. Calcium and phosphorus with smaller quantities of aluminum and iron were found in Schaumann bodies. Our studies indicate that organization of the asteroid body is more complex than hitherto described, independent of the centriolar and microtubular systems. Evidence for the possible developmental pathway of the Schaumann body is provided by morphological changes within myelinoid figures intimately related to the asteroid body.

Female↗

Prostaglandins and their precursors in rheumatoid arthritis: progress and problems.

Evidence is presented to support the hypothesis that prostaglandins and their precursors, collectively termed prostanoids, have an important role to play in the pathogenesis of joint destruction in arthritis, with particular reference to rheumatoid arthritis. After discussion of the role of prostanoids as mediators of inflammation, evidence is given that prostanoids are present in the joints of patients with rheumatoid arthritis, that these substances are capable of causing joint damage in vitro and in vivo, and that drugs which are able to arrest the progress of the arthritic condition or bring symptomatic relief possess the ability to inhibit prostanoid synthesis in vivo and in vitro.

Animals↗

Influence of nonsteroidal anti-inflammatory agents on lapine articular chondrocyte growth in vitro.

The lapine articular chondrocyte monolayer was used to study the effects of cell proliferation, morphology, nd synthesis of proteoglycans of four nonsteroidal anti-inflammatory agents piroxicam, diclofenac sodium, sulindac sulfiphe, and indomethacin. None of the substances caused any alteration to chondrocyte morphology. Cell proliferation and macromolecular binding of 35SO4 were unaffected by piroxicam (0.2, 2, and 20 micrograms/ml) or diclofenac sodium (0.2, 2, and 5 micrograms/ml). Whereas indomethacin markedly reduced cell proliferation (100 mumol/l; p less than 0.01), it failed to alter net proteoglycan synthesis significantly (1, 10, and 100 mumol/l). Sulindac sulfiphe significantly reduced chondrocyte proliferation at 0.5 and 5 micrograms/ml (p less than 0.01). The 0.5 micrograms/ml concentration also markedly stimulated proteoglycan synthesis (171%; p less than 0.01). The use of the articular chondrocyte monolayer as an experimental model to investigate drug-induced alterations of cartilage metabolism is discussed.

Animals↗

[Effect of piroxicam on the structure and function of joint cartilage].

Experimental studies on the dog were performed to investigate possible deleterious effects of non steroidal anti-inflammatory agents, in particular piroxicam, on healthy articular cartilage. Piroxicam, diclofenac, and indomethacin were administered orally to beagles over an 8-week period. Control animals received empty capsules during the same period. A variety of morphological investigations were carried out on the tissues of the knee joint following treatment. Macroscopically and at light microscopical level no differences in the structure of cartilage or synovial membrane were detected between control and test animals. Similarly, with the transmission electron microscope, no structural changes were observed between control and test groups (piroxicam-treated). The incorporation of radioactively labeled sulfur into cartilage proteoglycans was similar in piroxicam-treated and control dogs. Related studies involving the addition of piroxicam to isolated chondrocytes in vitro showed that the proliferative capacity and proteoglycan synthesis of chondrocytes were unaffected by this antirheumatic agent. It is concluded that piroxicam exerts no damaging effect on normal cartilage in the knee joint of the dog.

Animals↗

The relationship between DNA content, clinicopathology and prognosis in enteropancreatic carcinoids.

BACKGROUND/AIMS: The clinical behavior of carcinoid tumors is sometimes difficult to determine from their histological appearance. The aim of the present study was to evaluate whether the DNA distribution pattern seen in carcinoid tumors can be correlated with histopathological parameters and the patient's clinical course and prognosis. METHODOLOGY: The paraffin-embedded material of 44 enteropancreatic tumors underwent deparaffinization, was rehydrated, and mechanically and enzymatically processed into a single cell solution. For evaluation of the DNA histogram, analysis was performed with the help of an automatic single cell cytophotometric study. RESULTS: A correlation was seen between the DNA content and tumor stage (p = 0.01), radicalness of surgery (p = 0.03), tumor localization (p = 0.02) and patient's age (p = 0.05). In univariate analysis, patient's age (p = 0.04), tumor localization (p = 0.03), tumor stage (p = 0.0001), radicalness of surgery (p = 0.0006) and DNA content (p = 0.01) influenced prognosis. In multivariate analysis including these parameters, only tumor stage had an independent influence on prognosis. CONCLUSION: The clinical relevance of DNA measurement in carcinoid tumors is still unknown.

Adult↗

Prognostic relevance of histomorphological parameters and DNA content and their therapeutic consequences in esophageal carcinoma: a multivariate approach.

BACKGROUND/AIMS: Despite recent advances in surgical and multidisciplinary treatment, the prognosis for patients with esophageal carcinoma remains poor. The low prognostic accuracy of even surgical pathological TNM staging suggests that additional parameters would be useful in determining the prognosis. METHODOLOGY: We undertook a retrospective analysis of 115 patients who had undergone transhiatal and transthoracic esophageal resection due to squamous cell carcinoma of the esophagus. In addition to TNM classification and the usual morphological criteria, a quantitative DNS analysis using Image DNA cytometry was performed. At the time of DNA analysis, histomorphological parameters and survival time was not known. RESULTS: The main prognostic parameter was the curativity (R classification) of the operation. Using only patients who had had R0 resection, a multivariate analysis was performed. Parameters included: patient age; preoperative ASA classification; tumor localization; pN category; number of intra-thoracal lymph nodes removed; pT category; pM category; grading; lymphangiosis; ploidy; operative procedure, and the development of postoperative complications identifying the ploidy, and the depth of tumor infiltration of prognostically independent factors. CONCLUSIONS: In the case of a diploid or tetraploid DNA content, tumor resection is recommended even in the case of lymph node metastasis at the truncus coeliacus. Patients with a diploid or tetraploid tumor without distant metastasis and tumor stage pT1-pT3 may, after curative (RO) transthoracic resection with two-field lymph node dissection, have an advantage over patients having a transmediastinal procedure in terms of long-term follow up. In cases of aneuploid DNA content, tumor resection shows no advantage over palliative non-operative procedures. Preoperative radio- or chemotherapy may improve the prognosis of these patients.

Adolescent↗