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Biomedical subjects

A Hooper

Publications and source records attributed to A Hooper.

At least 19 recordsLinked to original sources

Aprotinin in the management of Achilles tendinopathy: a randomised controlled trial.

BACKGROUND: Achilles tendinopathy is a common condition, which can become chronic and interfere with athletic performance. The proteinase inhibitor aprotinin (as injection) has been found to improve recovery in patellar tendinopathy (evidence level 1b) and Achilles tendinopathy. Internationally this therapy is being used based on this limited knowledge base. AIM: To evaluate whether aprotinin injections decrease time to recovery in Achilles tendinopathy. METHOD: A prospective, randomised, double blind, placebo controlled trial was performed comparing saline (0.9%) plus local anaesthetic injections and eccentric exercises with aprotinin (30,000 kIU) plus local anaesthetic injection and eccentric exercise. Three injections were given, each a week apart. In total, 26 patients, with 33 affected tendons, were enrolled for this study. RESULTS: At no follow up point (2, 4, 12, or 52 weeks) was there any statistically significant difference between the treatment group and placebo. This included VISA-A scores and secondary outcome measures. However, a trend for improvement over placebo was noted. CONCLUSION: In this study on Achilles tendinopathy, aprotinin was not shown to offer any statistically significant benefit over placebo. Larger multicentre trials are needed to evaluate the efficacy of aprotinin in Achilles tendinopathy.

Achilles Tendon↗

Monoclonal antibody to vascular endothelial-cadherin is a potent inhibitor of angiogenesis, tumor growth, and metastasis.

Vascular endothelial-cadherin (VE-cad) is an endothelial cell-specific adhesion molecule that is crucial for proper assembly of vascular tubes. Here we show that a monoclonal antibody (BV13) directed to the extracellular region of VE-cad inhibits formation of adherens junctions and capillary-like structures by endothelial cells and blocks angiogenesis in the mouse cornea and in Matrigel plugs in vivo. Systemic administration of BV13 markedly decreases the growth of s.c. Lewis lung or human A431 epidermoid tumors and strongly suppresses the growth of Lewis lung metastases. These data demonstrate that VE-cad is essential for postnatal angiogenesis and thus validate VE-cad as a novel target for antiangiogenesis agents.

Animals↗

Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors.

Tumor angiogenesis is mediated by tumor-secreted angiogenic growth factors that interact with their surface receptors expressed on endothelial cells. Vascular endothelial growth factor (VEGF) and its receptor [fetal liver kinase 1 (Flk-1)/kinase insert domain-containing receptor] play an important role in vascular permeability and tumor angiogenesis. Previously, we reported on the development of anti-Flk-1 and antikinase insert domain-containing receptor monoclonal antibodies (mAbs) that potently inhibit VEGF binding and receptor signaling. Here, we report the effect of anti-Flk-1 mAb (DC101) on angiogenesis and tumor growth. Angiogenesis in vivo was examined using a growth factor supplemented (basic fibroblast growth factor + VEGF) Matrigel plug and an alginate-encapsulated tumor cell (Lewis lung) assay in C57BL/6 mice. Systemic administration of DC101 every 3 days markedly reduced neovascularization of Matrigel plugs and tumor-containing alginate beads in a dose-dependent fashion. Histological analysis of Matrigel plugs showed reduced numbers of endothelial cells and vessel structures. Several mouse tumors and human tumor xenografts in athymic mice were used to examine the effect of anti-Flk-1 mAb treatment on tumor angiogenesis and growth. Anti-Flk-1 mAb treatment significantly suppressed the growth of primary murine Lewis lung, 4T1 mammary, and B16 melanoma tumors and growth of Lewis lung metastases. DC101 also completely inhibited the growth of established epidermoid, glioblastoma, pancreatic, and renal human tumor xenografts. Histological examination of anti-Flk-1 mAb-treated tumors showed evidence of decreased microvessel density, tumor cell apoptosis, decreased tumor cell proliferation, and extensive tumor necrosis. These findings support the conclusion that anti-Flk-1 mAb treatment inhibits tumor growth by suppression of tumor-induced neovascularization and demonstrate the potential for therapeutic application of anti-VEGF receptor antibody in the treatment of angiogenesis-dependent tumors.

Animals↗

In situ expression of angiopoietins in astrocytomas identifies angiopoietin-2 as an early marker of tumor angiogenesis.

Angiopoietin-1 (Ang-1) and its naturally occurring antagonist angiopoietin-2 (Ang-2) are novel ligands that regulate tyrosine phosphorylation of the Tie2/Tek receptor on endothelial cells. Proper regulation of Tie2/Tek is absolutely required for normal vascular development, seemingly by regulating vascular remodeling and endothelial cell interactions with supporting pericytes/smooth muscle cells. We investigated the expression of Ang-1 and Ang-2 in human astrocytomas by in situ hybridization and compared them to the distribution of pericytes/smooth muscle cells by immunohistochemistry for alpha-smooth muscle actin (SMA). Ang-1 mRNA was localized in tumor cells and Ang-2 mRNA was detected in endothelial cells of hyperplastic and nonhyperplastic tumor vessels. Ang-2 was also expressed in partially sclerotic vessels and in vascular channels surrounded by tumor cells in brain adjacent to the tumor. Neither Ang-1 nor Ang-2 was detected in normal brain. Dynamic changes in SMA expression during glioma tumorigenesis appear to progress from fragmentation in early vascular hyperplasia to subsequent reassociation and enhanced expression in later stages of vascular proliferation in hyperplastic complexes in high-grade gliomas. All these vessels displaying dynamic changes in SMA immunoreactivity also expressed Ang-2 mRNA. Moreover, SMA immunoreactive intratumoral vascular channels lacking morphological evidence of hyperplasia also showed upregulation of Ang-2. These results suggest that angiopoietins are involved in the early stage of vascular activation and in advanced angiogenesis, and they identify Ang-2 as an early marker of glioma-induced neovascularization. The association between Ang-2 expression and alterations in SMA immunoreactivity suggests a role for Ang-2 in tumor-associated activation of pericytes/smooth muscle cells.

Angiopoietin-1↗

Post-traumatic and stress-induced osteolysis of the distal clavicle: MR imaging findings in 17 patients.

OBJECTIVE: To describe the MR imaging findings in patients with osteolysis of the distal clavicle and to compare the MR imaging appearance of clavicular osteolysis following acute injury with that related to chronic stress. DESIGN AND PATIENTS: MR imaging examinations were reviewed in 17 patients (14 men, 3 women; ages 16-55 years) with the diagnosis of post-traumatic or stress-induced osteolysis of the clavicle. A history of a single direct injury was present in seven patients and a history of weight-lifting, participation in sports, or repetitive microtrauma was present in 10 patients. RESULTS: MR imaging showed edema in the distal clavicle in 17 patients and, of these, eight also had edema in the acromion. The edema was most evident in STIR and fat-suppressed T2-weighted pulse sequences. Other findings about the acromioclavicular (AC) joint were prominence of the joint capsule in 14, joint fluid in eight, cortical irregularity in 12, and bone fragmentation in six patients. No differences in the MR imaging features of post-traumatic and stress-induced osteolysis of the distal clavicle were observed. CONCLUSION: Post-traumatic and stress-induced osteolysis of the distal clavicle have similar appearances on MR imaging, the most common and conspicuous MR imaging feature being increased T2 signal intensity in the distal clavicle.

Acromioclavicular Joint↗

Patients' explanatory models for heart failure and COPD exacerbations.

Although there is extensive information on the disease aspect of heart failure (HF) and chronic obstructive pulmonary disease (COPD), the illness aspect of these diseases has received limited attention. This limitation in our knowledge is of concern because these diseases are increasing in incidence and prevalence and contributing to the premature morbidity and mortality of thousands of persons. This naturalistic inquiry study was undertaken to describe the explanatory models (EMs) of persons hospitalized for HF (n = 30) or COPD (n = 30) exacerbations. In semistructured interviews, participants offered descriptions of the etiology, cause, and effects of their disease exacerbations and identified interventions that they believed would have helped prevent their hospitalizations or helped them to live better at home. The findings provide a basis for understanding the EMs of persons with HF or COPD as an initial step in making health care more relevant.

Adult↗

The dynamic progression of evolved character states for aromatic amino acid biosynthesis in gram-negative bacteria.

A systematic analysis of the evolution of aromatic amino acid biosynthesis in the Proteobacteria, previously focussed mainly upon the gamma subdivision, has now been extended to the beta subdivision. Five lineages were studied, represented by Neisseria gonorrhoeae, Nitrosomonas europaea, Alcaligenes faecalis, rRNA Group-III pseudomonads/Rubrivivax gelatinosus, and rRNA Group-II pseudomonads/Rhodocyclus tenuis. Within the phenylalanine pathway, the bifunctional P-protein (chorismate mutase/prephenate dehydratase) was present in each lineage and must have evolved in a common ancestor of the beta and gamma subdivisions. Each P-protein was found to be subject to activation by L-tyrosine, and to feedback inhibition by L-phenylalanine. Phenylalanine-inhibited (DS-phe) and tyrosine-inhibited (DS-tyr) isoenzymes of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase probably existed in the common beta-subdivision ancestor, with DS-tyr being lost in N. gonorrhoeae and A. faecalis. The participation of DS-phe in a dissociable multienzyme complex with one or more other common-pathway enzymes is known to exist in N. gonorrhoeae. The same complex is indicated by two peaks of DS-phe seen in chromatographic profiles of Group-III pseudomonads and A. faecalis. It is concluded that the contemporary DS-phe species present in subdivision gamma and beta must have had independent origins. Tyrosine biosynthesis was found to be quite diverse within the beta subdivision. Nit. europaea possessed an arogenate dehydrogenase which was specific for NADP+. In all other lineages, a broad-specificity cyclohexadienyl dehydrogenase (CHD) was present. In N. gonorrhoeae the CDH was specific for NAD+ while the remaining CDH species could utilize either NAD+ or NADP+. Only the CDH species within the rRNA Group-II pseudomonad/R. tenuis lineage was feedback-inhibited by L-tyrosine, and this correlated with an allosteric pattern where activation of the prephenate dehydratase component of the P-protein by L-tyrosine was relatively poor. However, the CDH enzyme present in N. gonorrhoeae and A. faecalis was subject to inhibition by 4-hydroxyphenylpyruvate, this being competitive with respect to the cyclohexadienyl substrate. The monofunctional species of chorismate mutase (CM-F) and cyclohexadienyl dehydratase, widely distributed among the gamma-subdivision assemblage and recently shown to be periplasmic enzymes, were demonstrated in Pseudomonas pickettii, a member of rRNA homology Group-II.

Alcaligenes↗

The displaced femoral neck fracture. Internal fixation versus bipolar endoprosthesis. Results of a prospective, randomized comparison.

The displaced femoral neck fracture poses difficult decision-making issues for the orthopedic surgeon. Young patients frequently require a rapid open reduction and rigid internal fixation in the face of multiple associated injuries. Elderly patients present the typical decision dilemma of internal fixation versus arthroplasty. Consecutive, randomized, prospective series of cases for evaluation of alternatives in the treatment of this difficult fracture are lacking. Between 1982 and 1984, 34 elderly patients with displaced femoral neck fractures were randomized to open reduction or hemiarthroplasty study groups. Although the surgical risks are relatively high, two-year observations showed better functional results in the cemented hemiarthroplasty group.

Aged↗

The prehistoric hand pictures at Gargas: attempts at simulation.

A number of experimental methods of reconstructing prehistoric hand images like those in the cave of Gargas, France, are described and assessed. The results of experiments using these methods are evaluated from the point of view of the bearing they have on our knowledge about the creation of the original pictures in the cave.

Art↗

Ro 21-7634, a new antiallergic agent with potent oral activity.

Ro 21-7634 was examined for oral antiallergic activity in two in vivo models commonly used to evaluate antiallergics. In the rat PCA test, this drug had an oral ID50 of 1.14 mg/kg and was found to be more potent than several other antiallergics including Disodium Cromoglycate (cromoglycate), Oxatomide, Doxanthrazole, Xanoxate, 2,6-bis (ethyoxyoxalylamino) pyridine, PRD-92-EA and M + B 22,948. In contrast to cromoglycate, Ro 21-7634 was found to be an orally active inhibitor of antigen-induced broncho-constriction in passively sensitized rats (ID50 = 0.2 mg/kg). In addition, Ro 21-7634 inhibited antigen-induced histamine release in an in vivo passive peritoneal anaphylaxis test system, following intraperitoneal administration. Ro 21-7634 demonstrated no end organ antagonism toward histamine, metacholine or serotonin in the guinea pig.

Administration, Oral↗

Further information on the prehistoric representations of human hands in the cave of Gargas.

This paper amends and adds recent information to Paul A. Janssens' earlier article on the prehistoric paintings of human hands in the cave of Gargas, France.1 Possible diagnoses for the deficiencies found in many of the hand pictures, and some non-medical theories of explanation, are reviewed. It is concluded that the hands used as stencils were mutilated and that the images were deliberately placed within the cave and were not the by-products of some other activity.

Anthropology, Cultural↗