Biomedical subjects

M Leunig

Publications and source records attributed to M Leunig.

54 records · Page 3Linked to original sources

PubMed1994

Angiogenesis and growth of isografted bone: quantitative in vivo assay in nude mice.

BACKGROUND: Understanding the regulation of vascularization and formation of bone after skeletal trauma is essential for the development of methods to promote healing. The lack of information on the biology of bone healing led us to establish an experimental model that facilitates the in vivo assessment of angiogenesis and growth of bone. EXPERIMENTAL DESIGN: Fresh, cryopreserved (frozen in the presence or absence of 10% dimethyl sulfoxide (DMSO)) or boiled neonatal femora were transplanted into dorsal skin fold chambers in adult mice of the identical strain, and angiogenesis and growth were monitored over 16 days. Computerized analysis of brightfield and epifluorescence images was employed to characterize the process of angiogenesis. Bone formation was quantified in vivo by the use of oxytetracycline. RESULTS: Reperfusion of pre-existing blood vessels of the graft was observed only in fresh transplanted femora, whereas femora of all experimental groups elicited angiogenic response from the host tissue. The rank order of the angiogenic response was: fresh > cryopreservation with DMSO > cryopreservation without DMSO > boiled. Growth of femora was completely abolished after cryopreservation or boiling. Only fresh transplanted femora increased in length (95 microns/day) and in cartilage diameter (41 microns/day). CONCLUSIONS: Our study demonstrates that (a) angiogenesis and growth of transplanted femora can be chronically assessed using in vivo microscopy; (b) the introduction of oxytetracycline for in vivo fluorescence microscopy allows the differential quantification of bone and cartilage growth; and (c) cryoprotection using DMSO enhances restoration of angiogenic potency after freezing. We consider this assay an excellent experimental model to study in vivo effects of agents or procedures that potentially modulate angiogenesis and growth of bone.

Animals↗

PubMed1993

Microvascular permeability of albumin, vascular surface area, and vascular volume measured in human adenocarcinoma LS174T using dorsal chamber in SCID mice.

A novel method was developed to measure the effective permeability of microvessels in three-dimensional tumors. Two unique features characterized our approach: (i) Texas Red (with peak excitation and peak emission wavelengths of 596 and 615 nm, respectively) was used for macromolecular labeling, to minimize the absorption of fluorescence light by hemoglobin in blood. Thus the tumor tissue could be treated approximately as a uniform medium with respect to light absorption. (ii) The light absorption and scattering in tumor tissues were accounted for in relating the fluorescence intensity to the amount of Texas Red-labeled macromolecules extravasated. The vascular permeability of Texas Red-labeled bovine serum albumin in human tumor xenograft LS174T implanted in dorsal skin-fold chamber in severe combined immunodeficient mice was measured using this method. The average permeability-surface area product per unit volume (PS/V, x 10(-4) sec-1) and the average effective permeability (P, x 10(-7) cm/sec) were found to be 1.26 +/- 0.72 and 6.06 +/- 4.30, respectively; the fractional volume of tumor vessels (Vves/V, %) was found to be 9.2 +/- 2.9, and the total surface area of vessels per unit volume (S/V, cm2/cm3) was found to be 239 +/- 82. The errors in the estimation of these parameters are discussed. The method described here is general and can be adapted to study the microvascular permeability of superficial tumors in various organs in patients or animals.

Adenocarcinoma↗

PubMed1993

Fluorescence photobleaching with spatial Fourier analysis: measurement of diffusion in light-scattering media.

A new method for the measurement of diffusion in thick samples is introduced, based upon the spatial Fourier analysis of Tsay and Jacobson (Biophys. J. 60: 360-368, 1991) for the video image analysis of fluorescence recovery after photobleaching (FRAP). In this approach, the diffusion coefficient is calculated from the decay of Fourier transform coefficients in successive fluorescence images. Previously, the application of FRAP in thick samples has been confounded by the optical effects of out-of-focus light and scattering and absorption by the sample. The theory of image formation is invoked to show that the decay rate is the same for both the observed fluorescence intensity and the true concentration distribution in the tissue. The method was tested in a series of macromolecular diffusion measurements in aqueous solution, in agarose gel, and in simulated tissue consisting of tumor cells (45% v/v) and blood cells (5% v/v) in an agarose gel. For a range of fluorescently labeled proteins (MW = 14 to 600 kD) and dextrans (MW = 4.4 to 147.8 kD), the diffusion coefficients in aqueous solution were comparable to previously published values. A comparison of the spatial Fourier analysis with a conventional direct photometric method revealed that even for the weakly scattering agarose sample, the conventional method gives a result that is inaccurate and dependent on sample thickness whereas the diffusion coefficient calculated by the spatial Fourier method agreed with published values and was independent of sample thickness. The diffusion coefficient of albumin in the simulated tissue samples, as determined by the spatial Fourier analysis, varied slightly with sample thickness. In contrast, when the same video images were analyzed by direct photometric analysis, the calculated diffusion coefficients were grossly inaccurate and highly dependent on sample thickness. No simple correction could be devised to ensure the accuracy of the direct photometric method of analysis.These in vitro experiments demonstrate the advantage of our new analysis for obtaining an accurate measure of the local diffusion coefficient in microscopic samples that are thick (thickness greater than the microscope depth of focus) and scatter light.

Biopolymers↗

PubMed1993

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.

In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.

Animals↗

PubMed1993

[Importance of increased interstitial fluid pressure in therapy of malignant tumors of the head-neck area].

Animal experiments showed that elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate supply of drugs to solid tumours. IFP is approximately 0 mmHg in most normal tissues. Up to now there have been only few studies showing elevated interstitial pressure in human tumours in situ: Mammary carcinomas, cervical carcinomas and colorectal cancers have an elevated IFP. We measured IFP in squamous cell carcinomas of the head and neck region in humans using the "wick-in-needle" technique. In all lesions (n = 25), the IFP was elevated (4-39 mmHg). The IFP increased with tumour size. The highest IFP was 39 mmHg in a 26 ml tumour. These results show that squamous cell carcinomas of the head and neck region in humans have an elevated interstitial fluid pressure. The elevation of IFP associated with inadequate delivery of drugs to the interstitium of malign tumours may reduce the response to therapy.

Carcinoma, Squamous Cell↗

PubMed1993

Dorsal skinfold chamber technique for intravital microscopy in nude mice.

For many years, observation chambers, implanted in various animal species and in man, have been used for intravital microscopy of the microcirculation in granulation tissue, preformed tissue, or of the microvascularization of tissue implants. We describe herein a skinfold chamber model for the intravital microscopic investigation of striated skin muscle in immunoincompetent, nude mice over a minimum period of 2 weeks. Using fluorescent markers for contrast enhancement of plasma (fluorescein isothiocyanate-dextran) and leukocytes (acridine orange), the presented model allows the quantitative analysis of 1) the microhemodynamic parameters microvessel diameter and red blood cell velocity in arterioles (16 to 50 mu diameter), capillaries (4 to 9 mu diameter), and post-capillary venules (19 to 60 mu diameter), 2) leukocyte/endothelium interaction in these vessel segments, 3) functional capillary density and intercapillary distance, and 4) endothelial cell integrity. These parameters can be assessed in the microcirculation of the striated muscle tissue under normal or pathological conditions, as well as in the microcirculation of transplanted xenogeneic (human) neoplastic and non-neoplastic tissue grafts.

Animals↗

PubMed1992

Angiogenesis, microvascular architecture, microhemodynamics, and interstitial fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice.

To date, most quantitative information on tumor angiogenesis, microcirculation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for the study of human tumor xenografts. Microcirculatory parameters in severe combined immunodeficient mice bearing a dorsal skin fold chamber preparation were quantified using intravital microscopy and image analysis. The take rate of the human colon adenocarcinoma LS174T in the chamber preparation was 100%, and the tumor area doubling time was 6.5 days. Three days following implantation of 2 x 10(5) tumor cells onto the striated skin muscle, capillary sprouts were noted in the tumor cell mass. Microvasculature in the tumors was established after 10 days. Capillary density, vessel diameter, red blood cell velocity, and blood flow rates in individual microvessels measured on days 10, 14, 18, and 22 showed no statistical difference in the striated muscle (capillaries) and subcutaneous tissue (arterioles and venules) of the skin of tumor-free animals (N = 6), whereas these parameters increased slightly, but not significantly, in the LS174T tumors (N = 7). Mean interstitial fluid pressure (+/- SD) in these small tumors was 4.6 +/- 1.7 mmHg (N = 4) on day 10 and 5.1 +/- 0.9 mmHg (N = 4) on day 22 and significantly elevated compared to that in the subcutaneous and skin tissue (-0.9 +/- 0.8 mmHg) (N = 4) (P < 0.001). To our knowledge, this is the first model enabling intravital microscopic studies of human tumor xenografts in a transparent chamber preparation in severe combined immunodeficient mice. Studies on angiogenesis, microcirculation, and transport using such a preparation should provide new insights into microcirculation-mediated mechanisms for cancer treatment.

Adenocarcinoma↗

PubMed1992

Interstitial hypertension in head and neck tumors in patients: correlation with tumor size.

Elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate delivery of drugs to solid tumors. IFP was measured in squamous cell carcinomas of the head and neck region in humans using the wick-in-needle technique. In all lesions (n = 19), the IFP was elevated (4-33 mm Hg). Furthermore, the IFP increased with tumor size. The highest IFP was 33 mm Hg in a 24-ml tumor. In one tumor, the IFP was found to be negative (-2.6 mm Hg), which is comparable to that in human skin or subcutaneous tissue. The histopathology of this tumor was benign. If this pressure difference between malignant and benign lesions can be confirmed in a large number of tumors, then the IFP could be used to aid tumor detection during needle biopsy. The value of IFP as a predictor of response to radiotherapy, photodynamic therapy, hyperthermia, and chemotherapy should be assessed prospectively.

Aged↗

PubMed1992

Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response.

Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to find out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100-150 mm3. Hyperthermia was induced by immersing the tumor in a water bath at 43 degrees C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P less than 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P less than 0.05 versus 43 degrees C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43 degrees C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy.

Animals↗

PubMedDate not supplied

Predictors of humeral head ischemia after intracapsular fracture of the proximal humerus.

The purpose of this study was to evaluate predictors of fracture-induced humeral head ischemia. Between February 1998 and December 2001, 100 intracapsular fractures of the proximal humerus, treated by open surgery, were included in a prospective surgical evaluation protocol (mean age, 60 years; minimum, 21 years; maximum, 88 years; 45 men; 57 right shoulders). Fracture morphology was assessed following a structured questionnaire and based on radiographic and intraoperative findings. Perfusion was assessed intraoperatively by observation of backflow after a borehole was drilled into the central part of the head in all shoulders and by intraosseous laser Doppler flowmetry in 46. Good predictors of ischemia were the length of the metaphyseal head extension (accuracy, 0.84 for calcar segments <8 mm), the integrity of the medial hinge (accuracy, 0.79 for disrupted hinge), and the basic fracture pattern (accuracy, 0.7 for combined types 2, 9, 10, 11, and 12). Moderate and poor predictors of ischemia were fractures consisting of four fragments (accuracy, 0.67), angular displacement of the head (accuracy, 0.62 for angulations over 45 degrees ), the amount of displacement of the tuberosities (accuracy, 0.61 for displacement over 10 mm), glenohumeral dislocation (accuracy, 0.49), head-split components (accuracy, 0.49), and fractures consisting of three fragments (accuracy, 0.38). When the above criteria (anatomic neck, short calcar, disrupted hinge) were combined, positive predictive values of up to 97% could be obtained. The most relevant predictors of ischemia were the length of the dorsomedial metaphyseal extension, the integrity of the medial hinge, and the basic fracture type determined with the binary description system.

Adult↗

PubMedDate not supplied

[Inadequate detectability of early stages of coxarthrosis with conventional roentgen images].

AIM: The study was undertaken to determine the value of standard radiographs in the early stages of osteoarthritis. METHODS: Standard radiographs and arthro-MRI's from thirty hips operated on for early arthrosis (age 25-57 years) were independently analyzed by two orthopaedic surgeons and one radiologist blinded from the intra-operative findings. The radiographs were read on two occasions two months apart. The radiographic findings were then compared to the intra-operative findings. RESULTS: Intra-operatively, all cases had a labral lesion and, in all but three of the cases, there was a major acetabular cartilage lesion. Each investigator diagnosed all of the labral and/or cartilage lesions on the arthro-MRI. However, on average, the investigators judged 20% (10-35%) of the hips to be normal on the standard radiographs. The probability of detecting an abnormal hip joint was statistically significantly better with arthro-MRI in four of six readings (p < 0.05) and there was a trend in favor of the arthro-MRI in the other two readings (p < 0.1). Intra-observer agreement when using the Tönnis classification of arthrosis on standard radiographs was 0.26 (-0.1-0.62), 0.69 (0.42-0.96) and 0.83 (0.53-1) [kappa-statistic, (95% confidence interval)]. The interobserver agreement was 0.24 (-0.07-0.55). CONCLUSION: Plain radiographs in the early stages of osteoarthrosis of the hip are neither reliable nor valid to diagnose the onset of disease. Therefore, in the case of a normal radiograph and clinical suspicion of arthrosis, a "normal" radiograph does not exclude the diagnosis and an artho-MRI should be obtained for further evaluation.

Adult↗

PubMedDate not supplied

[MR-Arthrography with radial sequences for visualization of early hip pathology not visible on plain radiographs].

AIM: We wanted to improve MRI visualization of early hip pathology invisible on plain radiographs. METHOD: An MR arthrography of the hip with radial sequences is described. The standard MR technique is improved by 1) using a small flexible surface coil to show selectively the hip joint to be examined, 2) application of gadolinium intra-articularly and 3) by radial imaging sequences perpendicular to the true plane of the acetabulum. CONCLUSION: By this technique it is possible to achieve an undistorted image of each aspect of the acetabular rim. Regions of special interest can be defined and their pathologies possibly related to morphologies of the proximal end of the femur.

Acetabulum↗

PubMedDate not supplied

Surgical landmarks to determine humeral head retrotorsion for hemiarthroplasty in fractures.

Malrotation has been suggested as a cause of failure of hemiarthroplasty of the proximal humerus. Placing a shoulder prosthesis in relationship to the bicipital groove might reproduce individual anatomy more reliably than using a standardized retrotorsion. The purpose of this study was to determine criteria for accurate adjustment of retrotorsion even when the proximal bicipital groove is destroyed, as is the case in fractures. The distance of the humeral head equatorial plane to the center of the bicipital groove was measured by high-resolution computed tomography at 4 levels (proximal and distal with 2 intermediate levels). The distal distance was considered to correspond to available references in fracture cases. The mean proximal distance was 8.0 mm (10th percentile, 6.2 mm; 90th percentile, 9.8 mm), and the mean distal distance was 8.5 mm (10th percentile, 7.1 mm; 90th percentile, 9.9 mm). As to the clinical relevance, there was no statistically significant difference between distances. For practical purposes in fracture indications, it is adequate to adjust the retrotorsion of the prosthetic component to the distal bicipital groove.

Arthroplasty↗

PubMedDate not supplied

Histopathology of cryopreserved bone allo- and isografts: pretreatment with dimethyl sulfoxide.

Partial graft cell survival and enhanced graft revascularization have suggested fast freezing using the cryoprotective substance dimethyl sulfoxide (DMSO) as a promising means to improve the biologic function and immune tolerance of allograft bone. This study determines the presence of osteoblasts (cola(1)(I) mRNA), osteoclasts (TRAP), and cytotoxic T cells (CTLs; GrA mRNA) within pretreated bone grafts 12 days after transplantation. The grafts were transplanted either as isografts, allografts, or allografts in presensitized recipients. In fresh isografts, serving as control, well-formed blood vessels and the highest numbers of viable osteoblasts and osteoclasts were found. In fresh allografts, blood vessels were observed within the marrow cavity and the bone was partially covered by osteoblasts and osteoclasts accompanied by CTLs. In DMSO-pretreated frozen allografts, blood vessels together with osteoblasts were observed in three of five, but in none of five grafts frozen without DMSO. However, infiltration with CTLs was higher in DMSO-pretreated frozen allografts when compared to grafts frozen without DMSO. In presensitized allograft recipients, independent of the pretreatment, in none of the grafts were either blood vessels or osteoblasts found. Thus, fast cryopreservation of bone using DMSO improves vascularization and expression of cola(1)(I) mRNA (osteoblasts) after allografting when compared to cryopreservation alone, potentially improving graft incorporation. As these grafts were still invaded by CTLs, the long-term effect of DMSO pretreatment needs to be defined.

Acid Phosphatase↗

PubMedDate not supplied

Entry point soft tissue damage in antegrade femoral nailing: a cadaver study.

INTRODUCTION: Little attention is paid to insertion site morbidity associated with antegrade femoral nailing. However, residual peritrochanteric pain after nailing is not uncommon. Additionally, the end branches of the medial femoral circumflex artery (m.f.c.a.) supplying the femoral head are in close proximity to the insertion site of the nail, and the occurrence of avascular necrosis of the femoral epiphysis after nailing in adolescents is rather frequent. OBJECTIVE: The aim of this study was to assess iatrogenic soft tissue injuries at the site of nail insertion. MATERIALS AND METHODS: Nailing with a reamed AO universal femoral nail was performed on sixteen adult cadavers followed by dissection of the proximal part of the femur to assess possible damage to the soft tissues. Three entry portals were defined. (A) entry portal lateral to the junction of the neck and the greater trochanter; (B) entry portal at the base of the greater trochanter anterior to a line along the longitudinal axis of the femoral neck; and (C) entry portal at the base of the greater trochanter posterior to a line along the axis of the femoral neck (at the piriformis fossa). RESULTS: In Group A, partial avulsion of the piriformis and the obturator internus tendon were present in four and in one of five specimens, respectively. Group B showed injuries to the piriformis tendon in two and to the gluteus minimus tendon in one of four cases. In Group C, partial avulsion of the piriformis, obturator internus, and obturator externus tendon were encountered in five, six, and two of seven specimens, respectively. Anterior branches of the ramus profundus of the m.f.c.a. within the synovial fold were damaged in all of these cases. CONCLUSION: To select the best nail entry portal, the ease of nail insertion must be weighed against the resulting soft tissue damage at the site of insertion. The nail entry portal at the piriformis fossa, although geometrically ideal and most recommended, causes the most significant damage to muscle and tendons as well as to the blood supply to the femoral head. Therefore, even if reported only once, the occurrence of avascular necrosis of the femoral head after nailing in adults is a possible complication of this nail entry portal. The authors therefore prefer to avoid this entry portal in every case. The nail entry portal anterior to the longitudinal axis of the femoral neck, as in group B, although better with respect to the soft tissue damage, has the worst geometric and biomechanical disadvantages. The results of the current study favor the nail entry portal lateral at the greater trochanter as in Group A, which is equal to the entry portal B with respect to the soft tissue damage but allows introduction of the nail into the medullar cavity without difficulties.

Bone Nails↗

PubMedDate not supplied

Effect of basic fibroblast growth factor on angiogenesis and growth of isografted bone: quantitative in vitro-in vivo analysis in mice.

Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To characterize the effect of bFGF on bone formation, whole neonatal murine femora were cultured in the presence or absence of bFGF and a neutralizing antibody against bFGF. In vitro, femoral elongation was provided by cartilage growth only; the calcified diaphyseal zone stained by oxytetracycline did not increase. When bFGF was added to the culture medium, longitudinal growth of the proximal and distal cartilage was inhibited in a dose-dependent manner (p < 0.05), and the number of hypertrophic chondrocytes in the growth plate was reduced. This phenomenon was absent in the presence of a neutralizing antibody, which when given alone significantly promoted femoral elongation. In contrast, in vivo after transplantation into adult mice bearing dorsal skin fold chambers, femora rapidly calcified after revascularization. This observation supports the notion that bone formation largely depends on angiogenesis-mediated events. To verify this hypothesis, angiogenesis and bone formation were quantified using bFGF known to be a stimulator of angiogenesis. Calcification of grafted femora was accelerated by bFGF given intraperitoneally. The neutralizing antibody slightly suppressed angiogenesis and femoral elongation (not statistically significant), whereas intravenous injections of both substances did not reveal a significant modulatory effect. In vivo the effect of systemically administered bFGF was inhomogeneous, but there was a strong correlation between angiogenesis and endochondral calcification (p < 0.001). These results suggest that exogenous bFGF modulates bone formation in vitro by inhibition of terminal differentiation of chondrocytes in the growth plate, and angiogenesis and concomitant in vivo events are pivotal in the promotion of rapid bone formation.

Animals↗

PubMedDate not supplied

Evaluation of photodynamic therapy-induced heating of hamster melanoma and its effect on local tumour eradication.

To investigate the contribution of hyperthermia on local tumour eradication by photodynamic therapy (PDT) we quantified PDT induced tumour heating and evaluated its biological effect in vivo. Syrian Golden hamsters bearing an amelanotic melanoma implanted into the dorsal skin received intravenous injections of Photofrin (5 mg kg-1). Twenty-four hours later tumours were illuminated by red light (630 nm; total energy: 100 J cm-2) at 100 and 200 mW cm-2 and tumour surface and tumour centre temperature were measured. The tumoricidally threshold temperature of 43 degrees C was exceeded at 200 mW cm-2 only, revealing a calculated equivalent treatment time at 43 degrees C of about 10 min. Melanomas treated by PDT at both light intensities disappeared within 48 h and did not reappear locally within the observation period of 32 days. Tumours treated by hyperthermia (water bath) at the maximum temperatures measured during illumination at 200 mW cm-2 (45.5 degrees C for 500 s) or animals receiving laser light at 200 mW cm-2 alone showed a significant growth delay compared to controls (p < 0.05), whereas illumination at 100 mW cm-2 alone or hyperthermia corresponding to the maximum temperature obtained at 100 mW cm-2 (39.5 degrees C for 1000 s) did not alter tumour growth. These data indicate that tumour temperature increased during PDT and exceeded the hyperthermic threshold temperature of 43 degrees C at 200 mW cm-2. In our tumour model hyperthermia was not necessary for a complete tumour eradication by PDT. Although a combination of PDT and hyperthermia might act in an additive or synergistic manner, an unrecognized overlap of both effects might complicate the interpretation of studies on the mechanisms of PDT.

Animals↗

PubMedDate not supplied

Basic fibroblast growth factor in serum and urine of patients with head and neck cancer.

Between 1996 and 1997 serum and urine levels of basic fibroblast growth factor (b-FGF) in patients with head and neck cancer were measured to answer the following questions: i) Are increased levels of b-FGF in serum and urine detectable in patients with malignant head and neck tumors? ii) Do these parameters correlate with tumor stage and differentiation of tumors? iii) Is there an association between growth behaviour (local or metastatic growth) and b-FGF levels in serum and/or urine? Eighty-nine patients with head and neck cancer as well as 45 patients with diseases unrelated to cancer were investigated. Detectable levels of b-FGF were found in the serum and urine of patients with malignant head and neck tumors. In addition, there was a significant correlation between tumor size and b-FGF levels in either serum or urine. No association of b-FGF concentrations with degree of histologic differentiation and tumor growth behaviour was observed. The results of this study demonstrate that b-FGF levels are elevated in serum and urine of patients with head and neck cancer. These findings suggest an involvement of b-FGF in the formation of solid tumors.

Biomarkers, Tumor↗