Deep femoral artery: A new point of view based on cadaveric study.

INTRODUCTION: In diagnostic angiographic procedures, the knowledge of arterial variations in the femoral artery (FA), deep femoral artery (DFA) and lateral and medial circumflex femoral arteries (LCFA, MCFA) has a great impact. MATERIAL AND METHODS: The frequency of branching patterns of these arteries was investigated in 111 thighs of body donors. Gender and side differences were analyzed statistically. RESULTS: The median distance of separation of the DFA from the FA in relation to the inguinal ligament (IL) was 3.29 cm. High origins (1-2 cm below IL) and middle origins (3-5 cm below IL) of the DFA were found in an equal distribution of 39.3% and 41.1%, respectively. Low origins (6-10 cm below IL) were rare (19.6%) but showed a tendential significance toward expression in males (p = 0.096). The origin of the LCFA from the FA (19.8%) or DFA (70.2%) are in line with the findings of other groups. The origin of the MCFA from FA (14.4%) or DFA (74.7%) showed that circumflex femoral arteries arose mostly from DFA. A trifurcation of the FA into the DFA, LCFA and MCFA was only observed in 9.9% and, therefore, less frequently than reported by others. Branches of the femoral nerve (FN) passed mostly anterior (46.4%) or anterior and posterior (47.8%) to the LCFA. The rare constellation of branches of FN passing only posterior to the LCFA (5.8%) showed a tendential significance to left side expression (p = 0.084). CONCLUSIONS: Taken together, this is the first classification of the median distance of separation of the DFA from the FA in relation to the IL in three defined groups. The knowledge of DFA branching pattern is essential for recent therapy options of cardiac diseases using a femoral artery access: transcatheter aortic valve replacement, catheter-based miniaturized ventricular assist device and veno-arterial extracorporal membrane oxygenation. The variant topography of the branches of FN in relation to LCFA should be kept in mind when harvesting an anterolateral thigh flap.

The gold industry standard for risk and cost of drug and vaccine development revisited.

Gold dimensions of pharmaceutical drug development indicate that it takes on average 11.9 years, with an investment around US$ 0.8 Billion, to launch one product on the market. Furthermore, approximately 22% of the drug candidates successfully complete clinical testing. These universally acknowledged proportions largely originate from one single, much cited publication; Dimasi et al. [5]. However an additional six articles describing new chemical entities (NCE) development were identified, which contain little, if any, information on vaccines. Published cumulative success rates range from 7% to 78% and investments calculations span US$ 0.8 to 1.7 Billion. Obviously this disserves further clarification?

[Functional anatomy of the larynx from clinical points of view: part II: Laryngeal mucous membrane, blood supply, innervation, lymphatic drainage, age-related changes]. / Update Larynx: funktionelle Anatomie unter klinischen Gesichtspunkten: Teil II: Kehlkopfschleimhaut, Blutgefässversorgung, Innervation, Lymphabfluss, Altersveränderungen.

Diseases of the larynx are of concern not only for ear, nose, and throat physicians and phoniatricians but also for other clinicians who treat the larynx either conservatively or surgically, including speech therapists, pediatricians, anesthetists, oncologists, pulmonologists, radiologists, and general practitioners. Based on today's state of knowledge and taking into account our own research results of the last years as well as clinical points of view, the present contribution gives a short overview of the anatomy and physiology of the larynx. Part 2 discusses the functional anatomy of the laryngeal mucous membrane (glycoconjugates, mucins, trefoil factor family peptides, antimicrobial substances, larynx-associated lymphoid tissue), the vascular supply, innervation, and lymphatic drainage, as well as age-related laryngeal changes and their effects on swallowing, breathing, and phonation.

[Functional anatomy of the larynx from clinical viewpoints. Part I: development, laryngeal skeleton, joints, insertion structures, musculature]. / Update Larynx: funktionelle Anatomie unter klinischen Gesichtspunkten. Teil I: Entwicklung, Kehlkopfskelett, Gelenke, Stimmlippenansatz, Muskulatur.

ENT specialist and phoniatricians are not the only professionals for whom diseases of the larynx occupy centre stage; this applies to those in all fields involving conservative or surgical treatment of the larynx, such as speech therapists, paediatricians, anaesthetists, oncologists, pulmonologists, radiologists and general practitioners. On the basis of current knowledge and taking account of results yielded by their own research in recent years and of clinical aspects, in this paper the authors give a short overview of basic knowledge on the anatomy and physiology of the larynx. Part 1 deals with its development and division, the laryngeal skeleton and joints, the insertion structures of the vocal folds and the laryngeal musculature and describes new insights into the mineralization and ossification of the laryngeal skeleton and their implications for phonation, arytenoid subluxation, degenerative joint changes and the biomechanics of vocal cord insertion.

Influence of estradiol on vascular endothelial growth factor expression in bone: a study in Göttingen miniature pigs and human osteoblasts.

Ovariectomy (OVX) in animal models is an accepted method to simulate postmenopausal osteoprosis. Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation, hypertrophic cartilage remodeling, ossification, and angiogenesis. We hypothesized that reduced VEGF expression in bone contributes to OVX-induced bone loss and tested it in a miniature pig model and in vitro using human osteoblasts. Seventeen primiparous sows (Göttingen miniature pigs) were allocated to two experimental groups when they were 30 months old: a control group (n = 9) and an OVX group (n = 8). After 15 months, VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay and verified by Western blot analysis. VEGF and its receptor (VEGFR) were localized by immunohistochemistry. Expression of VEGF mRNA was analyzed by real-time reverse-transcription polymerase chain reaction. Differently sulfated glycosaminoglycans were localized in subchondral bone histochemically. Osteoblasts were immunopositive for VEGF. VEGF concentration in the vertebra was 27% lower in OVX miniature pigs. VEGFR-2 could be immunostained on osteoblasts. VEGF mRNA and protein were detectable in the lumbar vertebrae of all animals. In subchondral trabecular bone of OVX animals, significantly more islands of mineralized cartilage containing chondroitin 4- and 6-sulfate or keratan sulfate occurred compared to the control group. The occurrence of remnants of mineralized cartilage in subchondral bone of the OVX group may be caused by a delayed bone turnover due to low VEGF levels. In vitro experiments revealed an increase of VEGF in the supernatant of osteoblasts after incubation with estradiol. In conclusion, estrogen seems to be a key factor for regulation of VEGF expression in bone. Loss of VEGF due to menopause may be a reason for reduction of bone density.

Molecular variation of Trypanosoma brucei subspecies as revealed by AFLP fingerprinting.

Genetic analysis of Trypanosoma spp. depends on the detection of variation between strains. We have used the amplified fragment length polymorphism (AFLP) technique to develop a convenient and reliable method for genetic characterization of Trypanosome (sub)species. AFLP accesses multiple independent sites within the genome and would allow a better definition of the relatedness of different Trypanosome (sub)species. Nine isolates (3 from each T. brucei subspecies) were tested with 40 AFLP primer combinations to identify the most appropriate pairs of restriction endonucleases and selective primers. Primers based on the recognition sequences of EcoRI and BglII were chosen and used to analyse 31 T. brucei isolates. Similarity levels calculated with the Pearson correlation coefficient ranged from 15 to 98%, and clusters were determined using the unweighted pair-group method using arithmetic averages (UPGMA). At the intraspecific level, AFLP fingerprints were grouped by numerical analysis in 2 main clusters, allowing a clear separation of T. b. gambiense (cluster I) from T. b. brucei and T. b. rhodesiense isolates (cluster II). Interspecies evaluation of this customized approach produced heterogeneous AFLP patterns, with unique genetic markers, except for T. evansi and T. equiperdum, which showed identical patterns and clustered together.

Immunohistochemical detection of estrogen receptor alpha in articular chondrocytes from cows, pigs and humans: in situ and in vitro results.

Clinical observations suggest that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis, but only little is known about the influence of these hormones on articular cartilage cells. The effect of estradiol is mediated by estrogen receptors alpha and beta. The goal of the present study was to search for estrogen receptor alpha in articular tissue from cows, pigs and humans by immunohistochemistry to form a basis for in vitro studies. In addition, we also tried to detect estrogen receptor alpha in cultivated articular chondrocytes from cows and bulls under certain culture conditions. Estrogen receptor alpha is detected by the use of antibody 13H2 in articular chondrocytes from cows, bulls, pigs and humans. Chondrocytes are physiologically exposed to reduced oxygen tension. In isolated articular chondrocytes from cows and bulls incubated either with 21% O2 or with 5% O2 positive cells were also found. These positive results therefore encourage testing the influence of estradiol on cultivated articular cartilage cells in these species under different culture conditions.

Evaluation of water content by spatially resolved transverse relaxation times of human articular cartilage.

Non-invasive assessment of cartilage properties, specifically water content, could prove helpful in the diagnosis of early degenerative joint diseases. Transverse relaxation times T(2) of human articular cartilage (34 cartilage slices of three donors) were measured on a pixel-by-pixel basis in a clinical whole body MR system in vitro. In vivo feasibility to measure quantitative T(2) maps was shown for human patellar cartilage. The relaxation times of cartilage with collagen in the radial zone oriented perpendicular to the magnetic field increased from approximately 10 ms near the bone to approximately 60 ms near the articular surface. Cartilage water content of the tibial plateau and femoral condyles could be determined from the correlation with T(2) (R(2) = 0.71) with an error of approximately 2 wt.%. In vivo, directional variation would need to be considered. If confirmed in vivo, T(2) measurements could potentially serve as a non-invasive tool for the evaluation of the status and distribution of water content in articular cartilage.

Matrix vesicles mediate mineralization of human thyroid cartilage.

Mineralization and ossification of human thyroid cartilage first starts after the end of adolescence when the previously cartilaginous human skeleton has become ossified and the epiphyseal discs are in the process of closing. However, the mechanisms involved in mineralization and ossification of human thyroid cartilage are not well understood. Ultrastructural analysis of human thyroid cartilage revealed that mineralization started close to cartilage canals in a matrix containing gigantic collagen fibers (asbestoid fibers). Matrix vesicles were detected in mineralized areas and were often associated with needle-like crystals. For the first time we were able to isolate matrix vesicles from human thyroid cartilage by mild enzymatic digestions and ultracentrifugation. These particles were oval and varied in size; some were heavily calcified. They were enriched in alkaline phosphatase, calcium, and inorganic phosphate, suggesting that the particles contain Ca2+-Pi complexes. Immunoblot analysis of these vesicles revealed the presence of annexins II, V, and VI, membrane-associated, channel-forming proteins, which allow influx of Ca2+ into the vesicles and intralumenal crystal growth. In addition, the vesicles were associated with types II and X collagen, suggesting that this association not only anchors the vesicles to the extracellular matrix, but, as shown previously, also stimulates Ca2+ influx into these particles. In conclusion, matrix vesicles isolated from human thyroid cartilage contain all the components, enabling them to initiate and mediate the mineralization process in human thyroid cartilage.

Laryngeal chondrosarcoma with regard to the ultrastructure.

Most common among the laryngeal sarcomas is the chondrosarcoma. The difficulties in differentiation between benign and malignant behavior of cartilaginous tumors are responsible for the danger of misinterpretation of chondrosarcoma as chondroma. A case of a laryngeal chondrosarcoma is presented examined by light and electron microscopy to determine if the ultrastructure of chondrosarcoma could be helpful in the correct diagnosis. The cells and their formation play a more important role than the extracellular matrix in the differentiation of tumor's behavior. As special criterias of malignancy by electron microscopy are the presence of dominant mitochondria, fat vacuoles, dilated rough endoplasmatic reticulum and the irregular shape of chondrocytes. The knowledge of the ultrastructure of chondrosarcomas may be helpful to distinguish between a benign chondroma and low-grade chondrosarcoma, especially when only small tumor biopsies are valuable.

Vascularization and cartilage mineralization of the thyroid cartilage of Munich minipigs and domestic pigs.

Thyroid cartilages of Munich minipigs and domestic pigs were investigated by polychrome sequential labeling, radiography, intravascular injections, histologic examination and scanning electron microscopy in order to gain further insight into the process of vascularization and cartilage mineralization. The relationship between vascularization and cartilage mineralization has only been studied in chondroepiphyses of long bones. Vessels branch off the perichondrial vascular network and enter parts of the thyroid cartilage with a large transverse diameter. Cartilage canals, which are perichondral invaginations, contain an arteriole, a venule, a capillary network and connective tissue. The capillaries form a glomerulus-like structure deep in the matrix of the cartilage. Neighbouring cartilage canals do not display any anastomoses. Cartilage mineralization occurs in large areas of the thyroid cartilage. It is only found in the interterritorial extracellular matrix. Mineralization of the cartilage is evident in areas supplied with cartilage canals as well as in non-supplied areas. Mineralized interterritorial matrix is composed of circular structures of different sizes fusing to form plaques. In scanning electron microscopy circular structures appear as globules. It is possible to visualize the dynamic process of cartilage mineralization with polychrome sequential labeling; it proceeds up to 4 microm per week. Distribution of cartilage canals reveals their nutritional role for the cartilage. According to investigations in chondroepiphyses, cartilage mineralization starts adjacent to the glomerular end of cartilage canals. In contrast, no correlation between cartilage vascularization and the beginning of cartilage mineralization of the thyroid cartilage of Munich minipigs and of domestic pigs has been found.

Effects of bedrest on deltoideus muscle morphology and enzymes.

To examine the effects of unweighting on the structural and metabolic adaptations of a non-postural muscle, deltoideus muscle biopsies were taken in seven male healthy subjects, before and after a 37 day bedrest. Myofibrillar ATPase histochemistry demonstrated no change in fibre type distributions (I, IIA, IIB), in fibre cross-sectional areas nor in capillary supply. No difference was noted in enzyme activities of oxidative metabolism (citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase), and glycolysis (hexokinase, lactate dehydrogenase). Electron microscopy showed a decrease in the volume density of lipids but no change in mitochondrial volume density and distribution. The results indicate that bedrest induces no major morphological and biochemical changes in deltoideus muscle, contrary to what was previously reported in vastus lateralis muscle. This lack of changes is probably related to an unaltered deltoideus muscle use.

[Chondrosarcoma of the larynx]. / Das Chondrosarkom des Kehlkopfes.

BACKGROUND: Manifestation of chondrosarcoma (CS) in the head and neck region is rare but it is the most frequently encountered non-epithelial malignancy of the larynx. Since this tumor entity is frequently neglected, its characteristics including differential diagnosis and therapy will be discussed in the following. PATIENTS: From 1975 to 1995, five cases with CS were diagnosed and treated in the Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel. RESULTS: The medical history of this five patients (one woman, four men, average age: 71 years) varied from 9 months to 10 years. Three patients had a fixation of the vocal cord; one patient had obviously reduced movement of the vocal cord. Two cases revealed a moderate and three cases a high differentiation in the histological examination. Initially one case was diagnosed as a chondroma. The origin of tumor growth was the cricoid cartilage in four patients and the cartilage of the arytenoid in one patient. Surgical treatment was either by partial or complete laryngectomy in two cases each. One patient refused any therapy. Two patients including the latter died of tumor related causes. CONCLUSIONS: Laryngeal CS grow slowly. Diagnosis is frequently made late in the course of disease. Obtaining of tissue for histological examination and diagnostic delimitation towards a chondroma can be difficult. Therapy depends on the degree of histological differentiation with radical excision of low or moderately differentiated CS and function preserving surgery in case of high differentiation.

Leiomyosarcoma of the larynx.

Leiomyosarcomas account for approximately 7% of all soft-tissue sarcomas and occur most frequently in the gastrointestinal tract and uterus. Leiomyosarcomas of the larynx are extremely rare with only about 27 cases reported in the available literature. We present a leiomyosarcoma of the left vocal cord that was treated by transoral CO2 laser surgery. To date, the patient has been free of disease for more than 25 months. Since these tumors may be difficult to diagnose, immunohistochemical studies may be necessary for making an unambiguous diagnosis. Primary treatment should be surgical resection, with small tumors suitable for partial laryngectomy or transoral laser surgery.

Effects of endurance training on oxidative capacity and structural composition of human arm and leg muscles.

Six healthy subjects performed endurance training of the same duration with legs and arms consecutively. Performance and muscle structure were measured before and after training in lower and upper limbs. Training induced similar increases in maximal oxygen consumption (6 +/- 1 vs. 7 +/- 2 mL min-1 kg-1: legs vs. arms, P > 0.05) and mitochondrial volume in leg and arm muscles (42 +/- 12 vs. 31 +/- 11%: legs vs. arms, P > 0.05). The gain in mitochondrial volume after training was achieved solely by increasing the fraction of mitochondria (+40 +/- 11%, P < 0.05) in the same muscle volume (+2 +/- 2%, P > 0.05) in the legs. In contrast, increased muscle volume (+14 +/- 3%, P < 0.05), in addition to a tendency for an increase in mitochondrial fraction (+16 +/- 11%, P > 0.05), occurred in the arms after training. Thus, similar improvements in muscle oxidative capacity in upper and lower limbs were brought about by different mechanisms. It is suggested that due to infrequent use and a lack of load-bearing function, arm muscle volume is underdeveloped in untrained, sedentary or detrained/injured subjects and that the mode of endurance training used in this study is sufficient to enlarge arm muscle volume as well as aerobic capacity.

Cartilage canals in human thyroid cartilage characterized by immunolocalization of collagen types I, II, pro-III, IV and X.

In this study the collagenous composition of cartilage canals in human thyroid cartilage, which are perichondral invaginations of blood vessels and connective tissue, and the surrounding cartilage matrix were investigated by immunolabelling with specific antibodies against type I, II, pro-III, IV and X collagen. During childhood and early adolescence no cartilage canals were detected in thyroid cartilage, and immunolabelling for type IV collagen was restricted to basal lamina components of blood vessels in the perichondrium. First immunolabelling for type IV collagen, belonging to blood vessels in cartilage canals, in both sexes was detected about the end of the second decade; it was localized in the dorsal part of the thyroid cartilage plate. At this time thyroid cartilage has already reached its final form and size. As revealed by von Kossa staining, vascularization preceded mineralization and ossification. In contrast to the male thyroid cartilage plate, no immunostaining for type IV collagen and no ossification was detected in the ventral half of female thyroid cartilage even in advanced age. The extracellular matrix of cells in cartilage canals showed positive immunostaining for collagen types I and pro-III as well as for collagen type II, indicating that the cells in the canal possess fibroblastic and chondrogenic properties. The extracellular matrix of hypertrophic chondrocytes adjacent to cartilage canals showed strong immunoreactivity for type X collagen. First mineralization was detected close to cartilage canals, suggesting that mineralization in human thyroid cartilage starts in the extracellular matrix adjacent to cartilage canals.

Design of the oxygen and substrate pathways. VI. structural basis of intracellular substrate supply to mitochondria in muscle cells.

This paper quantifies the structures involved in the transport and oxidation of carbohydrates and fatty acids within the muscle cell. The structural capacity is measured on whole-body random samples of the musculature of dogs and pygmy goats and compared with maximal rates of oxygen consumption and substrate oxidation. Comparing dogs and goats of the same body size provided a 1.55-fold difference in the maximal rate of oxidation when related to muscle mass. As in previous studies, we found that the volume of mitochondria was approximately proportional to aerobic capacity. The maximal glucose flux from intracellular stores to mitochondria is 1.6 times greater in the dog than in the goat; we find that the amount of glycogen stored in the muscle cells is 4.2 times as great in the dog, but part of the intracellular glycogen pool is used for anaerobic rather than for oxidative metabolism. The maximal fatty acid flux from intracellular stores to mitochondria is 1.5 times larger in the dog, and the amount of lipid stored is 2.3 times as great in the dog. Every lipid droplet is in direct contact with the outer membrane of a mitochondrion and the contact surface area is 3.6 times greater in the dog than in the goat. Additional measurements are needed to investigate the role of structural limitation at this step. The amount of substrates stored intracellularly in the muscle cells of the dog is about twice as much as would match the differences in the maximal rates of utilization. This allows the endurance-specialized dogs to run for longer periods at higher rates of oxidation.

Human quadriceps cross-sectional area, torque and neural activation during 6 months strength training.

Quadriceps muscle and fibre cross-sectional areas (CSA), torque and neural activation were studied in seven healthy males during 6 months of weight training on alternate days with six series of eight unilateral leg extensions at 80% of one repetition maximum. After training, the quadriceps cross-sectional area increased by 18.8 +/- 7.2% (P < 0.001) and 19.3 +/- 6.7% (P < 0.001) in the distal and proximal regions respectively, and by 13.0 +/- 7.2% (P < 0.001) in the central region of the muscle. Hypertrophy was significantly different between and within the four constituents of the quadriceps. Biopsies of the vastus lateralis at mid-thigh did not show any increase in mean fibre cross-sectional area. Maximum isometric voluntary torque increased by 29.6 +/- 7.9%-21.1 +/- 8.6% (P < 0.01-0.05) between 100 degrees and 160 degrees of knee extension, but no change in the optimum angle (110 degrees-120 degrees) for torque generation was found. A 12.0 +/- 10.8% (P < 0.02) increase in torque per unit area together with a right shift in the IEMG-torque relation and no change in maximum IEMG were observed. Time to peak isometric torque decreased by 45.8% (P < 0.03) but no change in time to maximum IEMG was observed. In conclusion, strength training of the quadriceps results in a variable hypertrophy of its components without affecting its angle-torque relation. The increase in torque per unit area, in the absence of changes in IEMG, may indicate changes in muscle architecture. An increase in muscle-tendon stiffness may account for the decrease in time to peak torque.

Localization of collagens and alkaline phosphatase activity during mineralization and ossification of human first rib cartilage.

The localization of type X collagen and alkaline phosphatase activity was examined in order to gain a better understanding of tissue remodelling during development of human first rib cartilage. First rib cartilages from children and adolescents showed no staining for type X collagen and alkaline phosphatase activity. After onset of mineralization in the late second decade, a peripheral ossification process preceded by mineralized fibrocartilage could be distinguished from a more central one preceded by mineralized hyaline cartilage. No immunostaining for type X collagen was found in either type of cartilage. However, strong staining for alkaline phosphatase activity was detected around chondrocyte-like cells within fibrocartilage adjacent to the peripheral mineralization front, while a weaker staining pattern was observed around chondrocytes of hyaline cartilage near the central mineralization front. In addition, the territorial matrix of some chondrocytes within the hyaline cartilage revealed staining for type I collagen, suggesting that these cells undergo a dedifferentiation process, which leads to a switch from type II to type I collagen synthesis. The study provides evidence that mineralization of the hyaline cartilage areas in human first rib cartilage occurs in the absence of type X collagen synthesis but in the presence of alkaline phosphatase. Thus, mineralization of first rib cartilage seems to follow a different pattern from endochondral ossification in epiphyseal discs.