[Acute mesenteric ischemia in a patient with relapsing polychondritis]. / Akuter Mesenterialinfarkt bei Polychondritis.

We report about a 43-year old woman with relapsing polychondritis, admitted with progressive malaise, fatigue, anorexia and profound weight loss. Two years ago a nasal chondritis with characteristic changes of the nasal profil, scleritis, laryngitis and unspecific general symptoms (fever, fatigue, signs of a systemic inflammation) developed and relapsing polychondritis was diagnosed. The patient was treated initially with azathioprine followed by methotrexate in combination with ciclosporine and glucocorticoids. During the hospitalization her condition slowly worsened, and crampy abdominal pain developed subsequently with massive tenderness, rebound and guarding. The clinically presumed diagnosis of ileus and peritonitis was radiomorphologically confirmed with signs of enteric perforation and a laparatomy was performed. A complete occlusion of the A. mesenterica superior and stenosis of the truncus coeliacus were diagnosed followed by a revascularization with an aorto-mesenteric bypass and subsequent resection of the necrotic ischemic ileum. An association with various autoimmune disorders including vasculitic syndromes is well known for relapsing polychondritis. The case demonstrated a progressive mesenteric ischemia with the acute exacerbation caused by a vasculitic mesenterial occlusion. The unusual presentation should be considered in the differential diagnosis of uncommon abdominal symptoms during the course of relapsing polychondritis.

[Establishment of an in vitro model for rheumatoid arthritis as test system for therapeutical substances]. / Etablierung eines in vitro Testsystems für die rheumatoide Arthritis zur Testung therapeutisch relevanter Wirkstoffe.

In our Tissue Engineering group a 3D in vitro model for rheumatoid Arthritis (in vitro pannus) was established with the aim to develop a standardized drug-screening test to analyze the effects of drugs and different biological substances. The advanced model consists of chondrocyte pellet cultures interacting with rheumatoid arthritis (RA) synovial cell cultures. To establish interactive 3D co-cultures defined rheumatoid arthritis synovial cell populations were centrifuged directly on chondrocyte pellet cultures. Histochemical stainings during time of co-culture revealed obvious invasion by RA synovial cell populations into the chondrocyte matrix. Gene expression analysis showed a downregulation of collagen type II expression in chondrocytes within 2 weeks after co-culture with RA synovial cells. Those interactive co-cultures allow the study of single cell populations as well as the cellular interactions in this system under in vitro conditions. Thus, the established co-culture model may be suitable for routine screening tests, which can be useful in supplementing animal experiments in basic research and drug testing.

Caracterización de 46 mujeres ancianas con cáncer de mama / Characterization of 46 elderly women with breast cancer

El cáncer mamario en mujeres ancianas es frecuente, a menudo se diagnostica en estadios avanzados y su tratamiento motiva controversias. Entre 1980 y 1994 estudiamos retrospectivamente 46 mujeres con esta condición. La edad promedio fue de 78 años (rango 70 a 89 años). La detección fue realizada por la paciente en 39 (85 por ciento) casos y en 7 (15 por ciento) por examen médico. la estadificación correspondió en un (2,2 por ciento) caso estadio I, 18 (39,1 por ciento) a II, 23 (50 por ciento) a III, y 4 (8,7 por ciento) a IV. El tamaño promedio clínico del tumor primario fue de 5,5 cm y el histopatológico de 4,95 cm. Se realizó cirugía conservadora en 3 (6,1 por ciento) casos, mastectomía radical modificada en 9 (18,4 por ciento), mastectomía simple extendida en 18 (36,7 por ciento), mastectomía simple en 10 (20,4 por ciento) mastectomía de aseo en 5 (10,2 por ciento), y no se operaron 4 (8.2 por ciento) casos. En 32 pacientes se practicó disección axilar encontrando metástasis nodales en 16 (50 por ciento). El tipo histológico más frecuente fue carcinoma ductal en 35 (71,4 por ciento) casos; de éstos el grado histológico fue II en 21 (61,8 por ciento) y III en 7 (20,6 por ciento) y el grado nuclear fue 2 en 22 (64,7 por ciento) y 3 en 6 (17,6 por ciento). El seguimiento promedio de la serie fue de 58 meses (margen 2 a 204 meses). Al cierre de esta revisión 11 (23,9 por ciento) pacientes están vivas sin enfermedad, 30 (65,2 por ciento) fallecieron (13 (43,3 por ciento) por su cáncer mamario, 10 (33,3 por ciento) por otras causas, 7 (23,3 por ciento) por causa desconocida) y en 5 (10,9 por ciento) se ignora su estado

Linfedema de miembro superior secundario al tratamiento de cáncer de mama / Lymphedema of upper extremity secondary to the breast cancer treatment

El linfedema de miembro superior es una complicación común del tratamiento del cáncer de mama que afecta aproximadamente al 20 a 25 por ciento de las pacientes. Las enfermas pueden padecer desde un aumento de volumen, dolor, tensión y pesadez en el miembro comprometido, llegando hasta la invalidez de éste. A menudo presentan infecciones cutáneas recurrentes. Por lo general este linfedema produce efectos lamentables en la calidad de vida de la mujer, sin embargo como se trata de una complicación no letal, recibe poca atención y se investiga menos que otras complicaciones del tratamiento del cáncer mamario. La etiología de linfedema es multifactorial y aunque está estrechamente relacionado con la linfadenectomía axilar y la radioterapia, aún se desconocen otros factores que contribuyen al establecimiento de esta condición y la naturaleza de la interacción de estos factores. No existe consenso respecto a la precisión de los métodos para evaluar el grado de edema del miembro superior aquejado y aún no se han desarrollado métodos exactos para evaluar el impacto funcional de esta complicación. El linfedema representa un problema de difícil manejo incluso con el advenimiento de modalidades del tratamiento modernas. Cuando se presenta inmediato a la terapia, suele resolverse durante las primeras semanas o meses del postoperatorio en un buen número de casos pero el crónico y tardío es de difícil solución. Algunas de las terapias actualmente en uso incluyen la elevación del miembro afectado, drenaje linfático manual, mangas elásticas, compresión neumática intermitente y tratamientos descongestionantes. Los tratamientos farmacológicos y quirúrgicos son controvertidos

Carcinoma diferenciado de tiroides: experiencia del Hospital de Valdivia / Thyroid differential carcinoma: experience at Hospital de Valdivia

Entre enero de 1978 y diciembre de 1996 se tratáron portadores de cáncer diferenciado de tiroides, 98 del tipo papilar y 4 del folicular. El grupo incluyó 86 mujeres y 16 hombres, con promedio de edad de 46,3 años (margen 9 a 80 años). De acuerdo a la clasificación de Meissner y Warren, 2 pacientes se estadificaron en estadio 0 (1,9 por ciento), 45 (44,1 por ciento) en estadio I;31 (30 por ciento) en estadio II; 17 (16,7 por ciento) en estadio IIIa; 1 (1,0 por ciento) en estadio IIIb y 6 (5,9 por ciento) en estadio IV. De los 102 pacientes, 100 fueron sometidos a tratamiento quirúrgico considerando el estadio de la enfermedad, tamaño del tumor primario y tipo histológico del carcinoma, priviligiando la cirugía conservadora en los cánceres papilares intracapsulares y la tiroidectomía total en los papilares extracapsulares y en los foliculares. Las complicaciones postoperatorias inmediata fueron 3 hematomas cervicales, 3 lesiones de nervio recurrente, 2 hipoparatiroidismo y otras menores, la mayoría de ellas secundarias a tiroidectomía total o casi total. No hubo mortalidad perioperatoria. La serie tiene un promedio de seguimiento de 74,1 meses. La sobrevida global es de 83,9 por ciento a 5 años y de 81,8 por ciento a 10 años, porcentaje que se mantiene hasta 20 años. En el estadio I la sobrevida es de 97,7 por ciento a 20 años

Emerging strategies of bone and joint repair.

The advances in biomedicine over the past decade have provided revolutionary insights into molecules that mediate cell proliferation and differentiation. Findings on the complex interplay of cells, growth factors, matrix molecules and cell adhesion molecules in the process of tissue patterning have vitalized the revolutionary approach of bioregenerative medicine and tissue engineering. Here we review the impact of recent work in this interdisciplinary field on the treatment of musculoskeletal disorders. This novel concept combines the transplantation of pluripotent stem cells, and the use of specifically tailored biomaterials, arrays of bioactive molecules and gene transfer technologies to direct the regeneration of pathologically altered musculoskeletal tissues.

Caracterización de 50 mujeres jóvenes con cáncer de mama / Characterization of 50 young women with breast cancer

El cáncer mamario en mujeres jóvenes es frecuente, difícil de diagnosticar y motiva controversias si es más agresivo que el de las mujeres de mayor edad. Entre 1989 y 1998 estudiamos retrospectivamente 50 mujeres jóvenes tratadas por esta neoplasia maligna. El promedio de edad fue de 35,2 años (margen 24 a 40 años). La detección fue realizada por la paciente en 43 (86 por ciento) casos, en 7 (14 por ciento) por examen físico y en 2 (4 por ciento) por mamografía. El tamaño promedio clínico del tumor primario fue de 4,6 cm (margen 1 a 17 cm) y el tamaño anatomopatológico fue de 3,79 cm (margen 1 a 15 cm). La axila fue clínicamente positiva en 22 (44 por ciento) pacientes e histológicamente positiva en 27 (55, 1 por ciento) de 49 casos evaluados. En 3 (6 por ciento) casos se encontró diseminación sistémica. De 44 mamografías realizadas, 29 (65,9 por ciento) sugirieron cáncer y las 32 citologías practicadas resultaron positivas. La estadificación correspondió en 7 (14 por ciento) casos al estadio I, 24 (48 por ciento) al II 16 (32 por ciento) al III y 3 (6 por ciento) al IV. Se realizó cirugía conservadora en 18 (34,6 por ciento) casos, mastectomía radical en 16 (30,8 por ciento) y simple extendida en 13 (25 por ciento). El estudio histológico de 49 casos reveló en 39 (79,5 por ciento) carcinoma canalicular; el grado histológico evaluado en 43 casos fue II en 19 (44,1 por ciento) y III en 20 (46,5 por ciento) y el grado nuclear de los mismos 43 pacientes fue 2 en 17 (39,5 por ciento) casos y I en 23 (53,4 por ciento). Con seguimiento promedio de 46 meses (margen 6 a 120 meses) 28 (56 por ciento) pacientes se encuentran vivas sin evidencias de enfermedad, 3 (6 por ciento) vivas con enfermedad y 19 (38 por ciento) han fallecido. Las características sobresalientes de las pacientes estudiadas fueron: detección de primario voluminoso, alto rendimiento diagnóstico de la citología para confirmar diagnóstico, e histológicamente tumores moderadamente o mal diferenciados y grados nucleares medianos o altos

The influence of transforming growth factor beta1 on mesenchymal cell repair of full-thickness cartilage defects.

To repair full-thickness articular cartilage defects in rabbit knees, we transplanted periosteal cells in a fibrin gel and determined the influence of transforming growth factor beta (TGF-beta) in vitro. Alginate served as a temporary supportive matrix component and was removed prior to transplantation. The defects were analyzed macroscopically, histologically, and electron microscopically, and evaluated with a semi-quantitative score system. Periosteal cell transplants showed a chondrogenic differentiation, which results in the development of embryonic-like cartilage tissue after 4 weeks and complete resurfacing of the patellar groove after 12 weeks. In the control groups, no repair was observed. Under the influence of TGF-beta1 we observed a reduction of the cartilage layer, whereas the osteochondral integration and the zonal architecture were improved. Periosteal cell-beads are stable cartilage transplants and have stiffness and elasticity enough for easy and sufficient transplant fixation. Further investigations are necessary to optimize the application of TGF-beta1 for cartilage repair.

Tissue engineered cartilage repair using cryopreserved and noncryopreserved chondrocytes.

The objective of this study was to reconstruct full thickness cartilage defects in rabbit knees with in vitro engineered cartilage tissue based on noncryopreserved and cryopreserved chondrocytes in polymer fleece scaffolds. Osteochondral defects in rabbits were filled with polymer cylinders with noncryopreserved or cryopreserved allogeneic chondrocytes and compared with empty defects and defects filled with polymers alone. The defects were evaluated macroscopically and histologically 4 and 12 weeks after surgery. Transplant samples were graded using a semiquantitative score system. Successful healing was defined as complete integration of a hyalinelike and structurally intact cartilage into the defect and occurred in 71% of the group with noncryopreserved chondrocytes after 4 weeks and 100% of the rabbit knees after 12 weeks, whereas hyalinelike cartilage was seen in 71% of the group with cryopreserved chondrocytes after 4 weeks, and in 85% after 12 weeks. No newly formed cancellous bone was present in the subchondral bone. In the control groups, no cartilagelike tissue was seen. Transplantation of chondrocytes in polymer fleece constructs is a suitable approach for joint cartilage repair. Noncryopreserved chondrocytes are preferred to cryopreserved chondrocytes because of their regenerative potential. In vitro engineered cartilage offers broad opportunities for optimization of cartilage transplantation based on the controlled use of morphogenic and biologically active factors such as transforming growth factor-beta and bone morphogenetic proteins.

Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits.

The biological bone healing depends on the presence of osteochondral progenitors and their ability for proliferation. Isolated periosteal cells were seeded into biodegradable PGLA polymer fleece or fibrin beads and cultivated for 14 days after prior monolayer culture. On 12 New Zealand white rabbits 8 mm metadiaphyseal ulna defects were created bilaterally and subsequently filled with cell-fibrin beads, with polymers seeded with cells compared to controls with fibrin beads and polymers alone and untreated defects. A semiquantitative grading score was applied for histomorphological and radiological analysis after 28 days. Histologically intense bone formation was observed in both experimental groups with cell transplants only. The histological and radiological scoring was superior for both experimental groups. Control groups revealed only poor healing indices and untreated defects did not heal. The highest histological score was noted in the group with polymer fleeces containing periosteal cells. Applying the radiographic score system we determined a significant difference between experimental groups and controls without cells. The radiographic and histological scores for both experimental groups containing periosteal cells differed not significantly. The results strongly encourage the approach of the transplantation of pluripotent mesenchymal cells within a suitable carrier structure for the reconstruction of critical size bone defects.

[Chondrocyte transplantation in PGLA/polydioxanone fleece]. / Chondrozytentransplantation in PGLA/Polydioxanon-Vliesen.

The transplantation of chondrogenic cells in a supportive carrier structure proved to be a promising alternative for the treatment of cartilage defects. In the study presented we focused on the transplantation of allogeneic chondrocytes in a biodegradable polymer scaffold (PGLA/Polydioxanon) in articular cartilage defects in a rabbit defect model. Isolated allogeneic chondrocytes embedded in a PGLA polymer scaffold were transplanted into osteochondrogenic defects of the patellar groove and compared with empty defects and transplants of polymer scaffolds without cells. The histological and histochemical analysis was performed after 4 and 12 weeks. The transplant integration and the architecture of the newly formed cartilage were evaluated with a semiquantitative score. After 4 weeks the development of a hyaline-like cartilage tissue of the cell-polymer-transplants was observed, after 12 weeks the defects were nearly completely filled with hyaline-like cartilage. The biodegradation of the polymer construct did not affect the histological structure of the transplant area. Defects of the groups with empty defect and polymer transplants without cells revealed no or insufficient healing indices. The study demonstrated that biodegradable polymers served as suitable carriers for the chondrocyte transplantation, which is due to the in-vitro establishment of a semi-solid cartilage transplant and the resulting effective transplant fixation into the defect. In-vivo the polymer cell transplants seem to provide a supportive microenvironment for the development of hyaline cartilage. The controlled release of morphogenic factors or bioactive molecules and the use of pluripotent mesenchymal progenitor cells opens new perspectives for the optimization of cartilage repair procedures.

Joint cartilage repair with transplantation of embryonic chondrocytes embedded in collagen-fibrin matrices.

OBJECTIVE: The objective of this study was to assess the feasibility of transplanting embryonic chondrogenic cells within a collagen-fibrin substrate for the reconstitution of full-thickness cartilage defects in chicken knee joints. METHODS: Full-thickness cartilage defects were created mechanically on the weight-bearing surface of the tibial condyle in 45 adult chickens and subsequently filled with chondrocytes embedded in a chondrocyte-collagen-fibrin gel. The transplants were compared to untreated defects and collagen-fibrin transplants without cells. The results were analyzed using histochemical and morphometrical methods after 3, 12 and 24 weeks. A semiquantitative histological grading system was applied to evaluate the transplant integration and the newly formed cartilage architecture. RESULTS: Chondrocyte-gel grafts developed to hyaline-like cartilage without any granulation tissue in the interface after 3 weeks. After 12 weeks the defects in the experimental group were filled completely with hyaline cartilage. The defects in the control groups in all cases healed with fibrous repair tissue. CONCLUSION: Fibrin-collagen gel allowed stable graft fixation and provided an adequate microenvironment for embryonic chondrocytes to generate hyaline-like neocartilage in a full-thickness cartilage defect.

Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix.

Use of multiplied viable cells from the nucleus pulposus in altered discs, following in vitro cultivation, may be a promising therapy for degenerative disc disease. Up till now, alginate has been used as a three-dimensional cell carrier to cultivate nucleus pulposus cells. However, the biocompatibility of the alginate, which depends on the composition and purity of alginate materials used, has not been considered for in vivo application so far. In this study, we cultured porcine cells from the nucleus pulposus in a mixture of fibrin and hyaluronic acid (HA). The DNA content and proteoglycan synthesis were compared to those measured in an alginate matrix. Although the increase in DNA content was 2.5-fold higher in the alginate culture after 3 weeks, the proteoglycan synthesis in relation to the DNA content was significantly higher in the fibrin/HA matrix. We found that the fibrin/hyaluronic acid matrix can be used as a substrate for in vitro cultivation.

Matrix-mixed culture: new methodology for chondrocyte culture and preparation of cartilage transplants.

For cartilage engineering a variety of biomaterials were applied for 3-dimensional chondrocyte embedding and transplantation. In order to find a suitable carrier for the in vitro culture of chondrocytes and the subsequent preparation of cartilage transplants we investigated the feasibility of a combination of the well-established matrices fibrin and alginate. In this work human articular chondrocytes were embedded and cultured either in alginate, a mixture of alginate and fibrin, or in a fibrin gel after the extraction of the alginate component (porous fibrin gel) over a period of 30 days. Histomorphological analysis, electron microscopy, and immunohistochemistry were performed to evaluate the phenotypic changes of the chondrocytes, as well as the quality of the newly formed cartilaginous matrix. Our experiments showed that a mixture of 0.6% alginate with 4.5% fibrin promoted sufficient chondrocyte proliferation and differentiation, resulting in the formation of a specific cartilage matrix. Alginate served as a temporary supportive matrix component during in vitro culture and can be easily removed prior to transplantation. The presented tissue engineering method on the basis of a mixed alginate-fibrin carrier offers the opportunity to create stable cartilage transplants for reconstructive surgery.

Procesos inflamatorios benignos de la mama / Benign inflammatory disorders of the breast

Los procesos inflamatorios benignos de la mama representan un capítulo importante en la patología de esta glándula. Afectan preferentemente a mujeres en edad fértil y el diagnóstico de algunas de estas lesiones puede resultar sencillo y su tratamiento no ofrecer dificultades, sin embargo en otros casos existen serios problemas, tanto para identificar el tipo de lesión como para determinar su adecuada conducta terapéutica. Afortunadamente, la mayoría de las lesiones inflamatorias mamarias finalmente demostrarán ser benignas. No obstante, el médico debe estar vigilante excluyendo en cualquier lesión la posibilidad de cáncer mamario. Cuando se enfrenta clínicamente una lesión sospechosa y su estudio no resulta totalmente clarificador, no debe postergarse la realización de una biopsia. En este artículo se revisan algunos conceptos sobre los procesos inflamatorios benignos más habituales de la mama, con especial énfasis en las bases del diagnóstico y las principales tendencias en su manejo y tratamiento

Heridas: conceptos generales / Wounds: general concepts

En la actualidad existen muchas definiciones y conductas ante los diferentes tipos de heridas, algunas con sólidas bases científicas y otras con arrastre histórico el cual, generalmente, es poco fundamentado. El propósito de este artículo es proporcionar una visión global, escrita y fotográfica del tema, que permita al médico general, evaluar y tipificar en forma expedita una determinada herida, decidir su tratamiento de urgencia y su manejo futuro

Joint cartilage regeneration by tissue engineering.

The research field of tissue engineering combines cells biology, biomaterial science, and surgery. Major long-term goals are tissue and organ replacement therapies using the patients' own cells. Our work is focused on the treatment of severe joint defects and on plastic surgery using in vitro engineered cartilage tissues. The practical approaches in cartilage engineering face problems with three-dimensional cell distribution or cell immobilization raising biocompatibility problems. The tissue engineering of cartilage is based on combining biocompatible cell embedding substances such as fibrin, agarose, alginate, hyaluronic acid and fiber fleece scaffolds of poly alpha-hydroxy acids (PLLA/PGLA). Different technical approaches were established: a) three-dimensional in vitro cultures of chondrocytes for the development of vital tissue transplants and b) interacting three-dimensional cultures consisting of different cell populations, such as BMP-transfected mesenchymal cells. The preshaped artificial tissue constructs were cultured in perfusion chambers to maintain a stable diffusion of nutrients during the in vitro pre-formation step. Subsequently, pre-formed tissues were implanted into nude mice and into 4 mm articular joint defects of rabbits. Transplants were found to produce cartilage typic morphological patterns and matrix. 80% of the transplants remained stable in vivo. However, 20% of the tissues are resorbed or replaced by a fibrous tissue. These results demonstrate that current artificial cartilage transplants are already feasible for plastic reconstruction. The treatment of severe joint defects, however, faces additional problems which are addressed in ongoing studies: (a) the fixation of engineered cartilage in joints, (b) the protection against chronic inflammatory degradation, and (c) the required enormous mechanical stability.

Bone engineering on the basis of periosteal cells cultured in polymer fleeces.

Large bone defects caused by severe trauma, infection or tumor resection are still a major challenge for orthopaedic surgery. The key concept for successful bone regeneration consists of combining the osteoinductive effect of osteogenic cells with a suitable carrier structure to promote osteoblastic differentiation and optimal matrix production. Therefore, periosteal cells cultured in polyglycolic-polylactid acid (PGLA) fleeces were investigated for their osteogenic differentiation and used to repair critical size bone defects in a rabbit model. Periosteal cells were isolated from New Zealand White rabbits and expanded in vitro. Osteogenic differentiation was investigated by analysis of alkaline phosphatase and osteocalcin production in vitro depending on culture conditions and passage number. Cells were seeded into PGLA fleeces. After further cultivation, tissue constructs were examined histologically and by immunohistochemistry for cell distribution and osteogenic differentiation. These constructs of defined size were used to repair critical size calvarial defects (group I) in rabbits compared to a defect repair with polymers only (group II) or to untreated defects (group III). Bone healing was evaluated after 4 weeks by radiodensitometry and a special histological scoring system. For early evaluation, radiodensitometry was not sensitive enough to detect differences in calcification. However, on histologic examination the group with cell/fleece constructs revealed intense formation of uncalcified bone. The mean defect closure of the experimental group I was 65%, compared to control groups II and III with 31% and 22%, respectively. The established methods of 3-D-cell culture and ex-vivo transplant assessment proved to be a valuable tool for quality assurance. The results demonstrate that the combination of periosteal cells and polymer fleeces is a tissue engineering approach, which may have clinical applications in various fields of reconstructive surgery.

Reconstrucción nasal / Nasal reconstruction

Se presenta la experiencia en construcción nasal del servicio de cirugía del Hospital Clínico Regional de Valdivia entre enero y noviembre de 1998. En este período se operaron 20 pacientes, el 60 por ciento correspondió a hombres y el 75 por ciento a mayores de 60 años. La etiología fue variada, siendo la oncológica la preponderante. La técnica quirúrgica varió desde el cierre primario hasta la reconstrucción con colgajos compuestos en dos tiempos y en su elección se consideraron varios factores, tales como edad sexo, patologías asociadas, etiología, superficie y ubicación del defecto. En la mayoría de los casos se utilizó sólo un tiempo quirúrgico. El porcentaje de complicaciones fue bajo (15 por ciento), todas de índole local y sin mayor gravedad, siendo el resultado estético y funcional bueno en todos los casos