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Biomedical subjects

P M Vogt

Publications and source records attributed to P M Vogt.

At least 19 recordsLinked to original sources

[Etiology, clinical aspects and therapy of penoscrotal lymphedema].

Penoscrotal lymphedema has serious functional, cosmetic, psychological and potentially malignant consequences. In contrast to the relatively common occurrence of this disease in areas with endemic filariasis, the incidence in the rest of the world is almost exclusively due to therapeutic sequelae of other illnesses or as congenital entities. As conservative forms of treatment have proved to be inefficient, we discuss different surgical options based on the treatment of 12 patients seen in our clinic. Only the complete excision of the edematous and fibrotic tissues, together with reconstructive methods using local flaps and skin grafts, can guarantee a definitive solution, irrespective of the etiology. A detailed anatomical knowledge of the regional lymphatic drainage pathways allows safe operative treatment. Despite the rarity of this disease, a number of different surgical procedures have been reported in the literature that are compared with the findings in our patients.

Adult↗

Patterns of expression and secretion of vascular endothelial growth factor in malignant soft-tissue tumours.

Vascular endothelial growth factor (VEGF) is an important cytokine especially in the process of tumour angiogenesis. A total of 46 soft-tissue sarcomas were analysed for the expression and possible secretion of VEGF by immunohistochemistry, in-situ hybridisation, and enzyme-linked immunosorbent assays (ELISA). VEGF was demonstrated immunohistochemically in tumour tissue in 45 of 46 cases. The detection of mRNA transcripts yielded evidence of synthesis of VEGF in these sarcomas. ELISA could be performed in 21 cases. Higher concentrations of VEGF were found in tumour-related intraoperatively sampled venous blood in 16 out of 21 patients (76%) than in systemic concentrations taken preoperatively. The results indicated the secretion of VEGF by tumour cells although these raised concentrations were not statistically significant. In 12 out of these 16 patients (75%) a concurrent moderate to strong immunoexpression of VEGF was detected. The relevance of VEGF blood concentrations as a potential "progress parameter" for the course of disease remains questionable. This is mainly due to the lack of statistical significance in the difference between systemic VEGF concentrations in patients and those of a control group. Further long-term follow-up studies are needed, which should include patients with tumour recurrences.

Adolescent↗

APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis.

Apart from its role in cell-adhesion, beta-catenin is regarded as an oncoprotein, the cytoplasmic level of which is regulated by APC as a tumor suppressor protein. Changes of chromosome 5q, the region that includes the APC-gene, are known to be important in the pathogenesis of fibromatosis; however, little is known about the significance of APC and beta-catenin in other mesenchymal tumors. Therefore, we used immunohistochemistry and DNA-analysis to investigate four cases of alveolar soft-part sarcoma (ASPS) as a mesenchymal tumor with a distinct histologic appearance. In three cases of ASPS the APC-gene product was found to have strong nuclear expression and only faint cytoplasmic staining. Beta-catenin showed a partly membranous, partly strong intracytoplasmic expression. No gene mutations for APC and beta-catenin were detected in any of the four cases. These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and beta-catenin play a role in the pathogenesis of soft tissue tumors such as ASPS. The significance of a striking nuclear accumulation of non-mutated, virtually functionally active APC-tumor suppressor protein has not yet been investigated. A nuclear function of APC in ASPS in down-regulating nuclear transcription processes linked to overexpression of beta-catenin, as is known in colorectal carcinogenesis, may be hypothesized.

Adenomatous Polyposis Coli Protein↗

Method for intraoperative positioning of the nipple-areola complex in vertical scar reduction mammaplasty.

The desired shape and position of the nipple-areola complex may be difficult to achieve in vertical scar reduction mammaplasty when using the standard technique of preoperative marking of the so-called mosque-shaped areolar pattern of excision. We describe our modified approach of intraoperative final positioning of the nipple-areola complex by hiding the nipple-areola complex behind the closed vertical incision. Individual positioning at the final part of the operation allows for more predictable results and also for a calculated lower positioning, which enables balance of the potential bottoming-out of the breast, particularly in previously large ptotic breasts. We believe that this modification helps to further improve the results of vertical scar reduction mammaplasty by adding more possibilities for shaping and "last-minute" modifications intraoperatively.

Adult↗

An innovative topical drug formulation for wound healing and infection treatment: in vitro and in vivo investigations of a povidone-iodine liposome hydrogel.

BACKGROUND: In topical wound treatment, the combination of anti-infectious therapy and a healing-promoting moisturization has not been accomplished yet. OBJECTIVE: Evaluation of a new topical drug consisting of a povidone-iodine (PVP-I) liposome hydrogel allowing for both antiseptic and moist treatment. METHODS: Pharmaceutical formulation of a complex of PVP-I (3%) and phosphatidylcholine in a hydrogel. In vitro, interaction of the complex with relevant micro-organisms was analysed by electron microscopy. Antimicrobial activity was investigated using Staphylococcus aureus in a suspension test. Tissue toxicity was examined by an explantation test in a rodent model. A randomized clinical study on efficacy and tolerability in wound healing was carried out on 35 patients with mesh grafts in parallel groups (PVP-I liposome hydrogel vs. Bactigras) for proof of concept in humans. RESULTS: A direct interaction of the PVP-I liposomes with micro-organisms by attachment to the cell surface was documented. A significantly better microbicidal activity and tissue tolerability of the PVP-I liposome hydrogel compared to conventional PVP-I formulations was shown. The results of the clinical study, especially measurements of neo-epithelization per time and transplant loss, demonstrate significant differences in favour of the PVP-I liposome hydrogel. CONCLUSION: The novel PVP-I liposome hydrogel combines microbicidal and wound healing activities resulting in enhanced epithelization.

Anti-Infective Agents, Local↗

[Clinical application of growth factors and cytokines in wound healing].

The clinical value of growth factor treatment of chronic wounds has yet to be determined. Beneficial effects have been reported so far only from specialized wound care centers where growth factors supplemented the results achieved with good wound care. In general optimization of current methods of external wound care, adequate metabolic and nutritional control and surgical measures should be employed before any adjuvant growth factor therapy is attempted. Current use of exogenously applied growth factors and cytokines appears to be reasonable only in the setting of controlled clinical studies according to the rules of "good clinical practice". With more knowledge on the biology of chronic wounds and progress in wound pharmacology the best application for these peptides will have to be reevaluated.

Animals↗

The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte colony-stimulating factor.

Severe injury causes immunosuppression. The main contributors are impaired leukocyte function and a cytokine dysbalance. GCSF increases PMN count, function and modulates the inflammatory response. However GCSF may overactivate leukocytes. The purpose of this study is to investigate whether GCSF is able to restore immune competence after severe injury. Lewis rats were divided into three groups: 30% TBSA burn + vehicle; 30% TBSA burn + GCSF (150 microg rhGCSF); Control. Blood samples were taken for total white cell count, PMNs, TNFalpha and IFNgamma. Leukocyte rolling and sticking were measured in the cremaster muscle microcirculation. Leukocyte diapedesis was investigated by lavage of the abdominal cavity and the lungs. Total white cell and PMN counts in the burn + GCSF group were significantly higher (P<0.001) than in burn+vehicle animals. Leukocyte adherence and diapedesis were not elevated in the burn + GCSF group as compared to the burn + vehicle group. TNFalpha (P<0.05) and IFNgamma (P<0.001) levels were significantly increased in the burn + vehicle animals compared to the burn + GCSF animals. GCSF modifies the immune system, as shown by an increase in white cell and PMN counts and by balancing the overall immune response from proinflammatory to normal, as shown by decreased TNFalpha and IFNgamma levels. GCSF does not overactivate PMNs.

Abdomen↗

[Prospects of tissue transfer and tissue culture].

Posttraumatic lesions of joints and extremities create a major challenge for an anatomic plastic reconstruction. The experimental and clinical progress in the field of tissue engineering, immunosuppression of allografts and xenografting including methods of genetic engineering provides a potential basis for the reconstruction of whole limbs or anatomical segments with living tissue.

Animals↗

[Use of growth factors in therapy of chronic wounds. Experimental, clinical and financial aspects].

Clinical trials on exogenous application of polypeptide growth factors in chronic wounds have not fulfilled the high expectations derived from results of experimental studies. There is no convincing evidence that growth factors may substitute for good wound care and efficient surgical approaches to wound closure. The ultimate goal of treatment of chronic ulcerations remains reconstitution of a durable skin envelope without unstable scarring. Therefore, optimization of current methods of wound therapy, including reconstructive vascular and plastic surgery and adequate metabolic and wound control, should be employed before any adjuvant growth factor therapy is attempted. As long as efficient and inexpensive therapy of chronic wounds by growth factors has not been demonstrated, empincal growth factor treatment should be rejected on scientific and economic grounds. Current use appears to be reasonable only under a regime of controlled clinical studies comparing growth factor treatment with conventional wound therapy and operative measures according to the rules of "good clinical practice".

Administration, Topical↗

Determination of endogenous growth factors in human wound fluid: temporal presence and profiles of secretion.

Growth factors are important substances in the central control of wound healing during the exudative phase. Although these peptides have been applied frequently to chronic wounds in clinical studies, little is known about the naturally occurring levels at the wound site in correlation to healing in superficial wounds. We have therefore investigated the presence of these cytokines in partial thickness wounds. In 16 patients undergoing reconstructive surgery, split-thickness skin wounds were enclosed in cutaneous vinyl chambers filled with 2.5 ml of saline. Chambers placed over unwounded skin served as controls. After 24 hours, the accumulated wound fluid was harvested and replaced by 2.5 ml of saline until the wounds were healed. Wound fluid was centrifuged, aliquoted, and frozen at -70 degrees C. Samples were analyzed for protein and growth factors (insulin-like growth factor-1, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor-AB, interleukin-1alpha, and transforming growth factor-beta1 and -beta2) and insulin-like growth factor-binding proteins 1 and 3 using a monoclonal Sandwich enzyme-linked immunosorbent assay and radioimmunoassay. All wounds healed in the liquid environment within 7 days (macroscopically) and 11 days (barrier function), respectively. In wound fluid, protein concentrations dropped from 5 mg/ml on day 1 to a baseline of 0.1 mg (unwounded skin), indicating a return of the barrier function. All growth factors could be measured already after 24 hours postwounding. However, the concentrations measured varied from 10 to more than 10,000 pg/ml between the different factors. The highest range was found for insulin-like growth factor-1 (21,000 to 41,000 pg/ml), the lowest for epidermal growth factor (3 to 63 and 3 to 88 pg/ml, respectively). Two different patterns of kinetics were distinguished: (1) a high initial peak decreasing to baseline values or below serum levels by the time of healing (insulin-like growth factor-1, insulin-like growth factor binding protein-1, -3, basic fibroblast growth factor, epidermal growth factor, platelet-derived growth factor-AB, transforming growth factor-beta1) and (2) a low initial concentration followed by an increase to a maximum at the time of epithelialization (interleukin-1alpha, transforming growth factor-beta2). Comparing the growth factor levels measured to serum baseline values, it was found that four of the growth factors appeared in wound fluid at above serum concentrations (interleukin-1alpha, transforming growth factor-beta2, basic fibroblast growth factor, epidermal growth factor); the other factors never reached serum values in wound fluid (insulin-like growth factor, transforming growth factor-beta1, platelet-derived growth factor-AB). It is concluded that the different profiles of secretion might reflect different functions of polypeptide growth factors such as stimulation of epithelialization (epidermal growth factor, insulin-like growth factor-1), matrix synthesis (transforming growth factor-beta), and inflammatory stimulation (interleukin-1alpha). The concentrations determined could serve as guidelines for adapted administration of growth factors once correlations to healing disorders such as overhealing and ulceration are established.

Adult↗

[Plastic reconstruction of the irradiated thoracic wall].

Chest-wall reconstruction following irradiation requires a surgical approach that addresses the specific healing disorders associated with irradiation: (1) biopsy of any open wound to rule out recurrence or persistence of tumor; (2) aggressive debridement of all necrotic or infected tissue, especially osteonecrosis of the chest wall; (3) reconstruction with well-vascularized muscle or musculocutaneous flaps. Coverage with muscle flaps provides a very reliable and effective single-stage reconstruction. Most types of flaps employed involve the latissimus, rectus abdominis and pectoralis muscle or musculocutaneous flaps. Rarely, stabilization of the thoracic wall is required, mostly facilitated by nonresorbable mesh. Respecting these principles, the irradiated chest wall can be reconstructed safely and with low morbidity. Plastic reconstructive techniques may also be employed safely to reconstruct the breast simultaneously in irradiated tissue by use of latissimus or rectus abdominis flaps.

Adult↗

[Thrombosis and tissue protection in microvascular surgery--an overview].

Although microvascular surgery has become a safer procedure in recent years, failure still occurs. The main cause of failure is thrombosis of the anastomosed vessels. Thrombosis involves the vascular wall, platelets and the coagulation system. Sometimes the transferred tissue dies with the anastomoses open. This is caused by an insufficient perfusion at the microcirculatory level, e.g. a reduction of capillary inflow by arteriolar vasoconstriction. Tissue damage also occurs after ischemia and reperfusion. Oxygen free radicals and activated leukocytes are responsible for this phenomenon. Thrombosis can be reduced by antiplatelet and anticoagulant drugs, substances increasing fibrinolysis and other agents. In the clinical situation, aspirin, heparin and dextrane have proven reliable. The microcirculation can be protected by aspirin. Reperfusion injury is affected with superoxide-dismutase, allopurinol and perfusion solutions. Future developments in this field will include locally applied antithrombotic agents and substances acting more specifically.

Anastomosis, Surgical↗

Dry, moist, and wet skin wound repair.

Effects of wet (saline in a vinyl chamber), moist (hydrocolloid dressing), and dry (sterile gauze dressing) environments on wound repair were studied in a porcine partial-thickness wound model. Chambers were exchanged and refilled daily with normal saline containing penicillin G (100 U/ml) and streptomycin (100 micrograms/ml). Hydrocolloid and gauze dressings were kept in place until biopsy of the wound site. Wounds in wet, moist, and dry environments were completely epithelialized on days 6, 7, and 8, respectively. Thickness of the epidermis in wet, moist, and dry wounds was 204 +/- 23, 141 +/- 12, and 129 +/- 18 (mean +/- SEM), respectively. Moist wounds had more subepidermal inflammatory cells than wet wounds. In comparison to dry wounds, the moist or the wet healing environment resulted in less necrosis and faster and better quality of healing in the formation of the newly regenerated epidermis.

Animals↗