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Biomedical subjects

M Chvapil

Publications and source records attributed to M Chvapil.

At least 73 records · Page 4Linked to original sources

A standardized animal model for evaluation of hemostatic effectiveness of various materials.

Two anatomic sites of bleeding injuries were selected in dogs to evaluate the hemostatic effectiveness and handling properties of various hemostatic materials. Split-thickness skin excisions inflict a wound of 90 cm2 area with regular spotted bleeding, which allows gravimetric quantitation of blood loss and of ease of removal of the agent. Excision of a wedge of the spleen 0.5 cm deep and 4 cm wide induced reproducible and moderate bleeding in pentobarbital-anesthesized dogs. Three to four similar injuries could be inflicted in the same spleen with comparable blood flow. In this model of bleeding injury only the highly effective hemostatic agents based on collagen and with a sheet-like structure successfully stopped the bleeding within 3 minutes. Powder-like collagen was effective only when pressed against the wound. Gelatin sponge or oxidized cellulose materials were less effective.

Animals↗

Immunoglobulins in hypertrophic scars and keloids.

Immunoglobulins A, G, and M were localized in normal skin, hypertrophic scars, keloids, and mature scars by the direct immunofluorescent antibody method. All three immunoglobulins appeared increased in the lesions above levels observed in normal skin. Extractions of the immunoglobulins from the same type of tissues also suggested an increase above levels from normal skin. The data suggest attritional leakage of several plasma proteins from the microvasculature in the lesions. No one immunoglobulin appears significantly increased in the lesions compared with others.

Albumins↗

A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia.

A phase I trial was conducted of the vitamin A derivative beta-all-trans-retinoic acid (vitamin A acid; TRA), delivered via a collagen sponge and cervical cap for mild or moderate intraepithelial cervical neoplasia. On the basis of known skin and mucosal membrane toxicity, a concentration of 0.05% TRA in a cream-based vehicle was selected as the starting dose and was escalated later with the use of a modified Fibonacchi scale. The delivery device and the TRA were changed daily for 4 days, and side effects were assessed on days 1, 2, 3, 4, 8, and 30 by clinical and colposcopic examination. Vaginal, cervical, and systemic toxicity were evaluated in 35 patients. No dose-related systemic effects were found; mild cervical inflammation increased in many patients at higher doses. Unacceptably high vaginal toxicity was reached at a TRA concentration of 0.484%. A concentration of 0.372% TRA is recommended for use in phase II trials in mild and moderate cervical intraepithelial neoplasia.

Biopsy↗

Evaluation of topically applied trans-retinoic acid in the treatment of cervical intraepithelial lesions.

The prevention and/or suppression of preneoplastic foci in animals has been convincingly demonstrated with the use of a variety of compounds, including retinoids. We report here a phase I/II trial of beta-trans-retinoic acid delivered via a collagen sponge/diaphragm insert for neoplasia of the cervix. Eighteen patients with biopsy-proved grades 2 and 3 cervical intraepithelial neoplasia underwent four consecutive daily applications of trans-retinoic aicd to the cervix. Conization of the cervix was performed 4 weeks later. Significant vaginal toxicity in 10 of 18 (55%) patients was unrelated to the concentration or carrying media of the drug. A reduction in size of the intraepithelial lesion was noted by colposcopy in six of 18 (33%) patients with complete resolution of disease at conization in two patients. A new delivery system designed to avoid vaginal toxicity while defining the optimal concentration and dosing schedule for these patients is currently under investigation.

Administration, Topical↗

Vascular manifestations in patients with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is clinically and genetically a heterogenous disorder of connective tissue synthesis. Seven clinical types of this disease have been identified and the underlying biochemical defects defined in types IV through VII. Unfortunately, most patients with major vascular complications of EDS have few, if any of the commonly recognized musculoskeletal and cutaneous abnormalities. Recognition of the correct diagnosis and the application of accepted vascular surgical techniques may improve the morbidity and mortality for these patients.

Adult↗

Considerations on manufacturing principles of a synthetic burn dressing: a review.

This review presents various considerations on the construction of a synthetic burn dressing, based mainly on collagen protein. Membranous wound covers are compared with sponge-felt types, monocomponental with composite. The importance of collagen crosslinking agent and the nonextractibility of any component from the dressing material are discussed. According to the type of the burn the dressing should be used dry or wet, plain or medicated, and changed often to reduce substantially the presence of necrotic tissue, inflammatory cell of the granulation tissue, and bacterial contamination.

Bandages↗

In vitro retinoid binding and release from a collagen sponge material in a simulated intravaginal environment.

Four in vitro preparations were constructed to simulate the intravaginal release of two retinoids, all-trans-retinoic acid (t-RA) and 13-cis-retinoic acid (c-RA), from a 0.7% collagen sponge diaphragm insert. Four t-RA concentrations, 0.019, 0.05, 0.1, and 0.15% in methanol were added to the sponge. The release into an artificial vaginal fluid was monitored serially over 72 h by serial analysis for t-RA and c-RA using high-pressure liquid chromatography. In each preparation, retinoid release was immediate and noncontinuous. At 37 degrees C, the retinoids were stable for at least 48 h. Trans-retinoic acid was the predominant retinoid recovered. Only trace amounts of the cis-isomer were released. Peak t-RA levels were 20 microM after 0.01%, 60-80 microM after 0.05%, 100-200 microM after 0.1%, and 320 microM after 0.15%. When the vaginal fluid bath was changed after 5 h, no further significant retinoid release occurred. There was significant loss of up to 70% of the applied t-RA into the collagen sponge. The retinoid binding was concentration dependent (higher binding with higher concentrations) and was maximal only after 24 h of co-incubation. The discontinuous release of t-RA and the high degree of binding to collagen would seem to preclude use of the diaphragm insert as a vaginal drug delivery system, at least for retinoids.

Biocompatible Materials↗

Altered activity in cultured cells caused by contaminants in tubes widely used for blood collection and serum preparation.

Cell culture has been recognized as an extremely sensitive system for measuring the toxicity of various materials. A study was done to determine whether the type of tube used to collect blood or store human serum might affect results in experiments requiring blood drawn into such tubes. In order to test tubes for contaminants that might alter cellular activity, a variety of commercially available tubes used for collection of blood and storage of serum were shaken while containing culture medium with fetal bovine serum. The medium was then applied to 3T3 fibroblasts in culture. Measuring incorporation of tritiated thymidine into DNA in log phase cells as an index of cellular proliferation, it was found that medium containing serum preincubated in tubes routinely used for blood collection could be extremely toxic. The same types of tube were also used to prepare human serum. When serum from some of the tubes was applied to 3T3 fibroblasts, a stimulatory effect was observed, perhaps caused by selective adsorption of inhibitory components of the blood or serum by various tubes. It is, therefore, crucial in a properly controlled experiment using serum in vitro to collect blood in tubes that exert no toxic or stimulatory effects in the assay or, at least, to be consistent in one's choice of tube. None of the tubes used for storage of serum showed significant effects in our assay.

Animals↗

Perivascular myofibroblasts and microvascular occlusion in hypertrophic scars and keloids.

Microvessels in normal skin, granulation tissue, hypertrophic scar, keloid, and mature scar from human subjects were studied by transmission electron microscopy. Comparative observations suggested that most microvessels in hypertrophic scar and keloid are occluded or partially occluded, apparently owing to an excess of endothelial cells. Endothelial cell contraction was also supported by the observations, and perivascular satellite cells (pericytes), some of which were identified as myofibroblasts, were observed in hypertrophic scars and keloids. Among findings from statistical analyses were that 1) the patency of microvessels in hypertrophic scar and granulation tissue is similar, as is that of microvessels in keloid and mature scar, but the patency of all these microvessels is significantly less than that of microvessels in normal skin, and 2) endothelial cell density is greater in nonpatent vessels than in patent vessels. The observed extent of microvascular occlusion supports a previously published theory that hypoxia is involved in the generation of hypertrophic scar.

Capillaries↗

Hypertrophic scars and keloids: a review and new concept concerning their origin.

Hypertrophic scars and keloids are often the sequelae of deep injury to the skin of man. These lesions are characterized by excessive collage, in the form of discrete nodules, and an excess of microvessels, most of which are partially or totally occluded due to an excess of endothelial cells. The occlusion contributes to a measurable hypoxia. Hypertrophic scars and keloids contain elevated levels of fibronectin, immunoglobulins, other plasma proteins, histamine, type III collagen and chondroitin-4-sulfate. PO2 levels are lower than in normal skin and PCO2 levels are higher. Granulation tissue from deep injury contains predisposed patterns for nodule formation, excessive numbers of fibroblasts, high levels of fibronectin, demonstrates excessive synthesis of fibroblast products and microvascular occlusion. The likely candidate for stimulating excessive numbers of fibroblasts is fibrin polymer which persists in all granulation wounds. The stimulator for excessive synthesis activity is postulated to be related to a state of hypoxia. We propose that resolution of the lesions would be effected when microvascular patency is restored and PO2 levels returned to normal. Degradation of excess collagen would take place when collagenase and/or lysosomal hydrolases would be unmasked, activated or released. The etiology of the hypertrophic scar and keloid (and thus their resolution) is believed to be directly related to the quality of the microvessels and the leakage and deposition of blood products into the wound and lesion.

Cell Membrane↗

Development of an infection-resistant vascular prosthesis.

To develop an infection-resistant arterial prosthesis, amikacin was bonded to 6-mm, uncrimped, filamentous velour prostheses using a collagen-release system. Infrarenal abdominal aortas were resected in 26 mongrel dogs. Thirteen dogs had their aortas replaced with the antibiotic-bonded grafts and 13 dogs had their aortas replaced with a graft containing collagen without antibiotics. Following closure of the abdominal incision, each dog received an intravenous infusion of 10(8) organisms of Staphylococcus aureus administered over a 30-minute interval. Three weeks after recovery from operation, the grafts were removed under aseptic conditions; all 13 (100%) of the control grafts were infected, but only one of 12 experimental grafts (8%) was infected. There were no adverse healing effects; to the contrary, there appeared to be accelerated development of a cellular neointima and fibroblastic infiltration to the interstices. Antibiotic bonding with a collagen-release system is a promising method for imparting infection resistance to a vascular prosthesis.

Amikacin↗