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M Leunig

Publications and source records attributed to M Leunig.

At least 37 records · Page 2Linked to original sources
PubMed1999

The connective-tissue envelope in revascularisation of patellar tendon grafts.

Free patellar tendon grafts used for the intra-articular replacement of ruptured anterior cruciate ligaments (ACL) lack perfusion at the time of implantation. The central core of the graft undergoes a process of ischaemic necrosis which may result in failure. Early reperfusion of the graft may diminish the extent of this process. We assessed the role of peritendinous connective tissue in the revascularisation of the patellar tendon graft from the day of implantation up to 24 days in a murine model using intravital microscopy. The peritendinous connective-tissue envelope of the graft was either completely removed, partially removed or not stripped before implantation into dorsal skinfold chambers of recipient mice. Initial revascularisation of the grafts with preserved peritendinous connective tissues began after two days. The process was delayed by five to six times in completely stripped patellar tendons (p < 0.05). Only grafts with preserved connective tissues showed high viability whereas those which were completely stripped appeared to be subvital. The presence of peritendinous connective tissues accelerates the revascularisation of free patellar tendon grafts.

Animals↗
PubMed1999

Quantitative assessment of angiogenesis and osteogenesis after transplantation of bone: comparison of isograft and allograft bone in mice.

We performed a vital microscopic study in mice bearing dorsal skinfold chambers to characterize microvascular perfusion and leukocyte/endothelium interaction and their effects on elongation and mineralization of neonatal isograft and allograft bone. Isograft (C57/BL to C57/BL) and allograft bone (C57/ BL to BALB/C) revascularized simultaneously. However, vascular perfusion and density were lower in allograft bone than in isograft bone. Leukocyte/endothelium interaction was the same in isograft and allograft bones. Revascularization was not detected in allograft bone transplanted to presensitized recipients. Moreover, in preexisting vessels at the transplantation site, leukocyte/endothelium interaction was altered in allograft bone of presensitized recipients, despite a normal systemic leukocyte count. Femoral growth resulting from thickening of both epiphyses did not differ between experimental groups, however, mineralization occurred in isograft bone only. Isograft bone was histologically intact, allograft bone hypovital and allograft bone in presensitized recipients necrotic 12 days after implantation. Our findings suggest that graft incorporation or rejection is mediated by the microvasculature and that presensitizing of recipients accelerates rejection of allograft bone.

Animals↗
PubMed1998

[The Bernese method of periacetabular osteotomy].

The periacetabular osteotomy is a strategy for the treatment of residual hip dysplasia in young adults with the aim of preventing secondary coxarthrosis. This polygonal, juxta-articular osteotomy respects the vascular blood supply to the acetabular fragment and thus facilitates an extensive acetabular reorientation with improvement of the insufficient coverage of the femoral head, including medial displacement of the fragment. All osteotomies are performed by one approach, the modified Smith-Petersen, which allows an anterior capsulotomy. Inspection of the joint not only provides information on acetabular rim pathologies, but also facilitates the control of impingement-free range of motion after the correction. The posterior column remains partially intact, allowing minimal internal fixation of the acetabular fragment and early mobilization similar to that after an intertrochanteric osteotomy. The dimensions of the true pelvis are unchanged, providing the capacity to have an unimpeded delivery in women. This paper describes the preoperative evaluation, current indications, surgical technique, postoperative care, and the results of this osteotomy.

Acetabulum↗
PubMed1998

A cement spacer for two-stage revision of infected implants of the hip joint.

We report the technical details and clinical results of twelve patients who had deep infections of implants in the hip joint and were treated by two-stage revision, using a gentamicin-loaded, hand-moulded cement spacer inserted for the period between resection and reimplantation arthroplasty. During management with the spacer, usually for 4 months, patients were almost free of pain and mobile with good leg control, spending 2/3 of the treatment period at home. Six of twelve spacers failed locally due to dislocation [5] or cement fracture [1], and more than two further episodes of surgery were required in 3 patients. Problems with dislocation of the spacer were significantly higher when the head to neck offset was lacking (P < 0.05) or when anchorage in the femoral shaft was poor. Nevertheless, infection after reimplantation arthroplasty did not occur by the time of follow-up (2.2 years). Based on these data, we consider that the use of the cement spacer is a promising approach to the treatment of complicated infections of the hip joint.

Aged↗
PubMed1997

Direct in vivo measurement of targeted binding in a human tumor xenograft.

Binding is crucial to the function of most biologically active molecules, but difficult to quantify directly in living tissue. To this end, fluorescence recovery after photobleaching was used to detect the immobilization of fluorescently labeled ligand caused by binding to receptors in vivo. Measurements of mAb affinity to target antigen within human tumor xenografts revealed a saturable binding isotherm, from which an in vivo carcinoembryonic antigen density of 0.56 nmol/g (5.0 x 10(5)/cell) and an association constant of Ka < or = 4 x 10(7) M(-1) were estimated. The present method can be adapted for in vivo studies of cell signaling, targeted drugs, gene therapy, and other processes involving receptor-ligand binding.

Animals↗
PubMed1997

[Fibroblast growth factor (b-FGF) in serum and urine of patients with head-neck malignancies].

BACKGROUND: The angiogenic peptide basic fibroblast growth factor (b-FGF) has been suggested to significantly promote angiogenesis; a central event for the growth and metastasis of solid tumors. Elevated levels of b-FGF in the serum and urine of patients with various types of cancer have been reported. No information exists about b-FGF levels in patients with primary head and neck cancer. The present study was performed to determine serum and urine levels of b-FGF in these patients. METHODS: b-FGF was quantified in the urine of 50 (62.5%) patients with head and neck cancer as well as 30 (37.5%) patients with diseases unrelated to cancer using an immunoassay with a detection limit of 1.0 pg/ml (FGF basic "Quantikine", DFB00. Biermann GmbH, Bad Nauheim, Germany). Urine was collected from patients before breakfast and centrifuged for 10 min at 1000 g. The supernatants were stored at -80 degrees C until the assay was performed. RESULTS: In the serum and urine of all patients, b-FGF was detectable by immunoassay. Cancer patients revealed significant increased serum b-FGF concentrations, in addition, advanced tumor size (T3/4) showed significant increased b-FGF levels in both serum and urine. There seems to be a correlation between serum b-FGF concentrations with degree of histologic differentiation. CONCLUSION: The results of this study demonstrate that b-FGF levels are elevated in serum and urine of patients with primary head and neck cancer. These findings suggest an involvement of b-FGF in the formation of solid tumors. The value of b-FGF as a non-invasive monitoring of treatment response in cancer therapy, the correlation with angiogenesis in histologic sections as well immunohistochemical detection are the aim of further investigations.

Adult↗
PubMed1997

Evaluation of the acetabular labrum by MR arthrography.

Since January 1993 we have carried out MR arthrography on 23 patients with clinical symptoms and signs of abnormality of the acetabular labrum. Most of the patients were young adults. Such symptoms are known precursors of osteoarthritis, and therefore early and accurate evaluation is required. We assessed the value of MR arthrography of the hip as a minimally-invasive diagnostic technique, in a prospective study and compared the findings with those at subsequent operations. All the patients complained of groin pain; 22 had a positive acetabular impingement test and 15 had radiological evidence of hip dysplasia. In 21 of the patients, MR arthrography suggested either degeneration or a tear of the labrum or both. These findings were confirmed at operation in 18 patients, but there was no abnormality of the labrum in the other three. In two of the patients, MR arthrography erroneously suggested an intact labrum. Both MR arthrography and intraoperative inspection located lesions of the superior labrum most often, and these appeared slightly larger on arthrography than at operation. We consider that MR arthrography is a promising diagnostic technique for the evaluation of abnormalities of the acetabular labrum.

Acetabulum↗
PubMed1997

Fractal characteristics of tumor vascular architecture during tumor growth and regression.

OBJECTIVE: Tumor vascular networks are different from normal vascular networks, but the mechanisms underlying these differences are not known. Understanding these mechanisms may be the key to improving the efficacy of treatment of solid tumors. METHODS: We studied the fractal characteristics of two-dimensional normal and tumor vascular networks grown in a murine dorsal chamber preparation and imaged with an intravital microscopy station. RESULTS: During tumor growth and regression, the vasculature in the tumor has scaling characteristics that reflect the changing state of the tissue. Growing tumors show vascular networks that progressively deviate from their normal pattern, in which they seem to follow diffusion-limited aggregation to a pathological condition in which they display scaling similar to percolation clusters near the percolation threshold. The percolation-like scaling indicates that the key determinants of tumor vascular architecture are local substrate properties rather than gradients of a diffusing substance such as an angiogenic growth factor. During tumor regression the fractal characteristics of the vasculature return to an intermediate between those of growing tumors and those of healthy tissues. Previous studies have shown that percolation-like scaling generally inhibits transport. CONCLUSIONS: In the present context, the percolation-like nature of tumor vasculature implies that tumor vascular networks possess inherent architectural obstacles to the delivery of diffusible substances such as oxygen and drugs.

Animals↗
PubMed1996

Tumor angiogenesis and interstitial hypertension.

Due to the high permeability of tumor vessels to fluids and plasma proteins, the microvascular pressure (MVP) is the principal driving force for interstitial hypertension in solid tumors; as a result, hydrostatic pressures between the microvascular and interstitial space are close to equilibrium. Based on these observations, we hypothesized that the tumor interstitial fluid pressure (IFP) should increase following the onset of angiogenesis. To this end, the relationship between IFP and tumor neovascularization was determined in the human colon adenocarcinoma (LS174T) and the murine carcinoma (MCaIV) implanted in a transparent dorsal skin fold chamber in severe combined immunodeficient mice. Three stages in the development of the tumor neovasculature were characterized by intravital microscopy. Stage I tumors were avascular, stage II was characterized by vascular sprouts and loops, and in stage III, the tumor vasculature was completely developed and blood flow was obvious. The IFP was measured with micropipettes and a servo-null system. For both tumor types, the IFP in stage I tumors was close to 0 mm Hg, and IFP increased significantly from one stage to the next. To further confirm that interstitial hypertension was associated with the development of the tumor vasculature, IFP was measured in LS174T spheroids. The mean pressure in spheroids was 0.2 +/- 0.3 mm Hg. In stage III tumors, the IFP was compared to the MVP. In MCaIV, the MVP was comparable to the IFP; however, in LS174T the MVP was significantly higher than the IFP. In conclusion, the results demonstrate that avascular tumors have atmospheric pressures and that tumor interstitial hypertension is associated with the development of the neovasculature.

Adenocarcinoma↗
PubMed1996

Heating or freezing bone. Effects on angiogenesis induction and growth potential in mice.

We have characterized the effect of bone graft treatment by heating or freezing (with or without dimethyl sulfoxide (DMSO)). Tissue culture and dorsal skin-fold chambers in mice were used as sites to quantify the effect on angiogenesis, growth and calcification of neonatal femora. Fresh femora increased in both length and cartilage diameter (calcification in vivo only), but cryopreservation or heating abolished the increase in femoral dimensions. In vivo, femora of all experimental groups elicited an angiogenic response from the host tissue, which was most pronounced for fresh femora, weaker for DMSO-preserved frozen bone and poor for unprotected frozen bone and boiled femora. Freezing in the presence of a cryopreservative (DMSO) was found to preserve the angiogenic potential of frozen bone, whereas unprotected heating or freezing significantly impaired angiogenesis induction and growth potential.

Animals↗
PubMed1996

Thermal necrosis after tibial reaming for intramedullary nail fixation. A report of three cases.

We present three young men who sustained closed diaphyseal fracture of the tibia and later developed severe osteocutaneous necrosis induced by heat during intramedullary reaming. They all had a narrow medullary cavity and in all a tourniquet had been used. Each developed a pretibial cutaneous blister soon after operation. In the following month severe osteomyelitis ensued, requiring segmental resection and osteocutaneous reconstruction.

Adolescent↗
PubMed1995

Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size.

Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvascular permeability to various macromolecules in the human colon adenocarcinoma LS174T transplanted in dorsal skin chambers in severe combined immunodeficient mice. These molecules were fluorescently labeled and injected i.v. into mice. The microvascular permeability was calculated from the fluorescence intensity measured by the intravital fluorescence microscopy technique. The value of permeability varied approximately 2-fold in the range of molecular weight from 25,000 to 160,000. These data indicate that tumor vessels are less permselective than normal vessels, presumably due to large pores in the vessel wall. The transport of macromolecules appears to be limited by diffusion through these pores. The cutoff size of the pores was estimated by observations of transvascular transport of sterically stabilized liposomes of 100-600 nm in diameter. We found that tumor vessels in our model were permeable to liposomes of up to 400 nm in diameter, suggesting that the cutoff size of the pores is between 400 and 600 nm in diameter.

Animals↗
PubMed1995

Quantitative analysis of angiogenesis and growth of bone: effect of indomethacin exposure in a combined in vitro-in vivo approach.

Nonsteroidal anti-inflammatory agents have been used experimentally and clinically to suppress a variety of physiological events, including angiogenesis and formation of bone. The exact mechanisms by which indomethacin alters skeletal tissue generation are unknown, due in part to methodological limitations. By the use of an organ culture assay and an animal model using intravital microscopy in mice bearing dorsal skinfold chambers, the effect of indomethacin on growth and angiogenesis of neonatal femora was characterized over 16 days. In both assays, femora significantly elongated with time (P < 0.05). The in vitro growth rate was more rapid than in vivo and dependent on the serum concentration, culture medium and age of mice. Although enhancing the serum content promoted cellular proliferation in organ culture, it dose-dependently suppressed femoral elongation, leading at 20% fetal calf serum to growth rates identical to those observed in vivo. Indomethacin supplementation (2 and 10 mg l-1) significantly accelerated longitudinal femoral growth in organ culture (P < 0.05), whereas in vivo indomethacin (2 mg kg-1) did not modulate either angiogenesis or elongation of bone. Our in vitro data propose a central role of serum in the regulation of bone formation. Although indomethacin altered femoral growth in vitro, our findings do not suggest that indomethacin suppresses angiogenesis or growth of bone in vivo. The complexity of physiological events in vivo may be obscuring a detectable effect.

Animals↗
PubMed1994

Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft.

Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenocarcinoma LS174T xenograft were quantified by using the dorsal skin-fold chamber implanted in severe combined immunodeficient mice and intravital fluorescence microscopy. Significant extravascular accumulation was the dominant feature of liposome distribution in tumors, whereas only minimal intramural accumulation in postcapillary and collecting venules was observed in normal s.c. tissue. The extravasated liposomes in tumors distributed heterogeneously and formed perivascular clusters that did not move significantly and could be observed for up to 1 week. The effective permeability of tumor vessels to liposomes (2.0 +/- 1.6 x 10(-8) cm/s; n = 23) was six times smaller than that to bovine serum albumin (1.2 +/- 0.5 x 10(-7) cm/s; n = 6). These results provide new insights into the mechanisms of transendothelial pathways of liposomes and improvements in liposome-mediated drug delivery.

Adenocarcinoma↗
PubMed1994

Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice.

Simultaneous measurements of intravascular and interstitial oxygen partial pressure (PO2) in any tissue have not previously been reported, despite the importance of oxygen in health and in disease. This is due to the limitations of current techniques, both invasive and noninvasive. We have optically measured microscopic profiles of PO2 with high spatial resolution in subcutaneous tissue and transplanted tumors in mice by combining an oxygen-dependent phosphorescence quenching method and a transparent tissue preparation. The strengths of our approach include the ability to follow PO2 in the same location for several weeks and to relate these measurements to local blood flow and vascular architecture. Our results show that (i) PO2 values in blood vessels in well-vascularized regions of a human colon adenocarcinoma xenograft are comparable to those in surrounding arterioles and venules, (ii) carbogen (95% O2/5% CO2) breathing increases microvascular PO2 in tumors, and (iii) in unanesthetized and anesthetized mice PO2 drops to hypoxic values at < 200 microns from isolated vessels but drops by < 5 mmHg (1 mmHg = 133 Pa) in highly vascularized tumor regions. Our method should permit noninvasive evaluations of oxygen-modifying agents and offer further mechanistic information about tumor pathophysiology in tissue preparations where the surface of the tissue can be observed.

Adenocarcinoma↗
PubMed1994

Photodynamic therapy-induced alterations in interstitial fluid pressure, volume and water content of an amelanotic melanoma in the hamster.

The effect of photodynamic therapy (PDT) on interstitial fluid pressure (IFP), tumour volume and water content was measured in melanomas grown in hamsters. Unlike control tumours, treated tumours exhibited a 40-60% increase in volume at 1, 3 and 6 h post PDT. IFP also increased at 1 and 3 h after PDT, but decreased to 50% of control value after 24 h, presumably as a result of PDT-induced microcirculatory impairment.

Animals↗