Giant cell fibroblastoma: a variant of dermatofibrosarcoma protruberans treated with Mohs' micrographic surgery.
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Adult↗
Biomedical subjects
J L Cook
Publications and source records attributed to J L Cook.
Correlation of ultrasound and magnetic resonance imaging with clinical outcome after patellar tenotomy: prospective and retrospective studies. Victorian Institute of Sport Tendon Study Group.
OBJECTIVE: To report the appearances of ultrasound (US) and magnetic resonance imaging (MRI) before and after surgery for chronic patellar tendinopathy and to correlate postoperative appearances with clinical outcome. DESIGN: A 12-month prospective longitudinal study and a retrospective study, each part using different patients. Prospective study included clinical assessment, ultrasound, and MRI all performed before and 12 months after surgery. Retrospective study included ultrasound and clinical assessment only (i.e., no MRI) 24 to 67 months after surgery. SETTING: Institutional athlete study group in Australia (Victorian Institute of Sport Tendon Study Group). PATIENTS: In the prospective study, 13 patients (all male; 15 tendons) who underwent patellar tenotomy; in the retrospective study, 17 different patients (18 tendons) who had undergone identical surgery. MAIN OUTCOME MEASURES: Ultrasound and MRI appearances and clinical assessment at baseline and 12 months after surgery (prospective study). Ultrasound appearance and clinical assessment 24 to 67 months after surgery (retrospective study). Dimensions of abnormal regions on imaging were measured. Clinical assessment included categorical rating and numerical Victorian Institute of Sport Assessment (VISA) score. RESULTS: In the prospective study, preoperative ultrasound and MRI appearances confirmed the clinical diagnosis of patellar tendinopathy. Postoperative ultrasound and MRI also revealed abnormalities consistent with patellar tendinopathy. Despite this, 11 of 15 (73%) tendons were rated clinically as either good or excellent. Imaging modalities were unable to distinguish tendons rated as good or excellent from those rated poor at 12 months. In the retrospective study, ultrasound images revealed abnormalities despite full clinical recovery. There was no correlation between dimension of ultrasound abnormality and either VISA score or time since surgery. CONCLUSION: After open patellar tenotomy, MRI and ultrasound findings remain abnormal despite clinical recovery. Thus, clinicians ought to base postoperative management of patients undergoing patellar tenotomy on clinical grounds rather than imaging findings. At present, there appears to be no role for routine postoperative imaging of patients recovering slowly after patellar tenotomy. However, this is not to suggest that imaging cannot play a role in special circumstances.
Adolescent↗
Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury.
Heme oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury. In this study, we examined whether exogenous administration of HO-1 by gene transfer could also confer protection. We first demonstrated the feasibility of overexpressing HO-1 in the lung by gene transfer. A fragment of the rat HO-1 cDNA clone containing the entire coding region was cloned into plasmid pAC-CMVpLpA, and recombinant adenoviruses containing the rat HO-1 cDNA fragment Ad5-HO-1 were generated by homologous recombination. Intratracheal administration of Ad5-HO-1 resulted in a time-dependent increase in expression of HO-1 mRNA and protein in the rat lungs. Increased HO-1 protein expression was detected diffusely in the bronchiolar epithelium of rats receiving Ad5-HO-1, as assessed by immunohistochemical studies. We then examined whether ectopic expression of HO-1 could confer protection against hyperoxia-induced lung injury. Rats receiving Ad5-HO-1, but not AdV-betaGal, a recombinant adenovirus expressing Escherichia coli beta-galactosidase, before exposure to hyperoxia (>99% O2) exhibited marked reduction in lung injury, as assessed by volume of pleural effusion and histological analyses (significant reduction of edema, hemorrhage, and inflammation). In addition, rats receiving Ad5-HO-1 also exhibited increased survivability against hyperoxic stress when compared with rats receiving AdV-betaGal. Expression of the antioxidant enzymes manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (CuZn-SOD) and of L-ferritin and H-ferritin was not affected by Ad5-HO-1 administration. Furthermore, rats treated with Ad5-HO-1 exhibited attenuation of hyperoxia-induced neutrophil inflammation and apoptosis. Taken together, these data suggest the feasibility of high-level HO-1 expression in the rat lung by gene delivery. To our knowledge, we have demonstrated for the first time that HO-1 can provide protection against hyperoxia-induced lung injury in vivo by modulation of neutrophil inflammation and lung apoptosis.
Adenoviridae↗
Histopathology of common tendinopathies. Update and implications for clinical management.
Tendon disorders are a major problem for participants in competitive and recreational sports. To try to determine whether the histopathology underlying these conditions explains why they often prove recalcitrant to treatment, we reviewed studies of the histopathology of sports-related, symptomatic Achilles, patellar, extensor carpi radialis brevis and rotator cuff tendons. The literature indicates that healthy tendons appear glistening white to the naked eye and microscopy reveals a hierarchical arrangement of tightly packed, parallel bundles of collagen fibres that have a characteristic reflectivity under polarised light. Stainable ground substance (extracellular matrix) is absent and vasculature is inconspicuous. Tenocytes are generally inconspicuous and fibroblasts and myofibroblasts absent. In stark contrast, symptomatic tendons in athletes appear grey and amorphous to the naked eye and microscopy reveals discontinuous and disorganised collagen fibres that lack reflectivity under polarised light. This is associated with an increase in the amount of mucoid ground substance, which is confirmed with Alcian blue stain. At sites of maximal mucoid change, tenocytes, when present, are plump and chondroid in appearance (exaggerated fibrocartilaginous metaplasia). These changes are accompanied by the increasingly conspicuous presence of cells within the tendon tissue, most of which have a fibroblastic or myofibroblastic appearance (smooth muscle actin is demonstrated using an avidin biotin technique). Maximal cellular proliferation is accompanied by prominent capillary proliferation and a tendency for discontinuity of collagen fibres in this area. Often, there is an abrupt discontinuity of both vascular and myofibroblastic proliferation immediately adjacent to the area of greatest abnormality. The most significant feature is the absence of inflammatory cells. These observations confirm that the histopathological findings in athletes with overuse tendinopathies are consistent with those in tendinosis--a degenerative condition of unknown aetiology. This may have implications for the prognosis and timing of a return to sport after experiencing tendon symptoms. As the common overuse tendon conditions are rarely, if ever, caused by 'tendinitis', we suggest the term 'tendinopathy' be used to describe the common overuse tendon conditions. We conclude that effective treatment of athletes with tendinopathies must target the most common underlying histopathology, tendinosis, a noninflammatory condition.
Anti-Inflammatory Agents, Non-Steroidal↗
Internet use by endocrinologists.
Endocrinologists, like other physicians, are information managers. They manage both disease-specific and patient-specific information and must integrate both types of information to provide the best possible care for their patients. New technologies offer abundant new approaches to medical information management tasks. Many will focus on computer hardware and software applications; others will seek solutions from video, telecommunications, the marriage of computer and consumer electronics, and other evolving technologies popularly referred to as multimedia and virtual reality. Few innovations in history have had the potential to so profoundly change our lives as the Internet. The incredible growth of the Internet to a vast system of interconnected networks serving more than 75 million users in the United States alone largely has been driven by the growth of newsgroups and e-mail, providing a means of communication among Internet users and particularly the World Wide Web (WWW). Information on web pages can be "linked" so that users can click on a link and navigate to other information on the same page, on other pages of the same document, on other files on the same computer, or on other computers linked to the Internet anywhere in the world. Moreover, the navigation requires no knowledge of arcane, difficult-to-remember commands. Hypertext links have the great utility of allowing users to navigate through information according to their own interests and information needs, as opposed to those of an author. The WWW also allows authors to link to other sources of information, rather than having to recreate it themselves. Increasingly easy access to the WWW has dramatically reduced the barriers to publication of information, since it is much easier and much less expensive to place information on the WWW than it is to publish and distribute it in hard copy form. This ease of publication has led to an incredible proliferation of information on the WWW. Much WWW information is of value to health professionals, including endocrinologists. This chapter reviews a variety of potential uses of the Internet by endocrinologists in their clinical, research, and educator roles and provides a number of examples of each. Approaches to finding useful information on the Internet are addressed. Finally, we include some speculation about the role of the Internet in the future practice of endocrinology.
Decision Making, Computer-Assisted↗
Progesterone and prostaglandin H synthase-2 involvement in alcohol-induced preterm birth in mice.
BACKGROUND: Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P4) and prostaglandins have been shown to play important roles in parturition in both human and animal models. Recently, it has been suggested that prostaglandin H synthase-2 (PGHS-2) is responsible for prostaglandin changes associated with term and preterm labor. It is possible that alcohol induces preterm birth by altering P4 or PGHS-2 levels. These studies were designed to determine the role of P4 and PGHS-2 in alcohol-induced preterm labor in mice. METHODS: Experiment 1: Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at various times in gestation up to the time of delivery. Plasma P4 levels were measured by radioimmunoassay and uterine PGHS-2 mRNA expression was measured by Ribonuclease Protection Assay. Results indicated that alcohol treatment was associated with an earlier decline in plasma P4 levels and an earlier rise in uterine PGHS-2 mRNA levels during gestation. Experiment 2: Pregnant C57BL/6J females were treated with either P4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragastrically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Results indicate that P4 pretreatment effectively antagonized alcohol-induced preterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mg/kg nimesulide (a specific PGHS-2 inhibitor) or vehicle (saline) subcutaneously, 2 hr before treatment with either 6 g/kg alcohol (given intragastrically) or isocaloric sucrose. Nimesulide was effective in antagonizing alcohol-induced preterm labor. CONCLUSIONS: Together, these data suggest that both P4 and PGHS-2 may play roles in alcohol-induced preterm birth.
Animals↗
In vitro effects of glucosamine and acetylsalicylate on canine chondrocytes in three-dimensional culture.
OBJECTIVE: To determine effects of glucosamine and acetylsalicylate on canine chondrocytes in 3-dimensional culture. SAMPLE POPULATION: Chondrocytes isolated from articular cartilage of 2 adult female dogs recently euthanatized for reasons unrelated to orthopedic abnormalities. PROCEDURE: Chondrocytes were cultured in a 3-dimensional agarose-based medium alone (control), with glucosamine (100 microg/ml; GL), or with acetylsalicylate (18 microg/ml; AS). Supernatant and agarose plugs from 4 wells/group/d were collected on days 3, 6, and 12 of culture. Agarose plugs were evaluated for percentage of viable cells, percentage of cells producing pericellular or territorial matrix, glycosaminoglycan (GAG) concentration, and type-II collagen production. Prostaglandin E2 concentration in supernatants was determined. RESULTS: Chondrocytes in all groups had characteristics indicative of viability and differentiation; however, on day 12, a lower percentage of viable cells was detected in the AS group, compared with the other 2 groups. On day 6, GAG concentration in the AS group was significantly greater than concentrations in the other 2 groups. On day 12, GAG concentrations in the GL and AS groups were significantly less than in the control group. Within the GL and AS groups, cell viability was significantly less on day 12, compared with day 3. Significant differences in PGE2 concentration among or within groups and evidence of type II collagen production were not detected. CONCLUSIONS: 3-dimensional culture of canine chondrocytes allows for production of hyaline cartilage matrix constituents and growth of cells with morphologic characteristics similar to those of articular cartilage. Acetylsalicylate and glucosamine, at the single concentration evaluated, had detrimental effects on chondrocyte viability, GAG production, or both.
Animals↗
Temporal changes in gene expression following cryogenic rat brain injury.
Expression of 18 genes was examined at 8 different time points between 1 h and 28 days following cryogenic rat brain injury. The genes include thymidine kinase (TK), p53 tumor suppressor, c-fos, renin, myelin basic protein (MBP), proteolipid protein (PLP), transferrin, transferrin receptor, platelet-derived growth factor A (PDGF A), platelet-derived growth factor B (PDGF B), platelet-derived growth factor receptor alpha (PDGF alpha receptor), platelet-derived growth factor receptor beta (PDGF beta receptor), glial fibrillary acidic protein (GFAP), transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-1 (FGF-R1), insulin-like growth factor-1 (IGF-1), and somatostatin. Time courses of gene expression were determined for RNAs derived from hippocampus and cortex. Genes were divided into categories based upon those in which statistically significant changes in expression were first observed at or before 24 h (early genes) and those in which changes were first observed at or after 72 h (late genes). In the present model, many genes demonstrate elevated RNA levels in the cortex prior to hippocampus, following injury. RNAs transcribed from late genes tend to be elevated concurrently in cortex and hippocampus.
Animals↗
Ethanol and parturition: a role for prostaglandins.
A common pattern of birth defects was reported in children born to alcoholic women over 20 years ago. Shortly thereafter the constellation of defects became known as the Fetal Alcohol Syndrome, and reports from around the world served to acknowledge the pervasiveness of the disorder. Simultaneously with the clinical reports, animal models were developed to characterize the full spectrum of the teratogenic effects of ethanol. Not only did these animal models serve to define the actions of ethanol on fetal growth and development at the molecular pharmacological, neuroanatomical, and behavioral level, but unintentionally, they have resulted in renewed scientific interest in the effects of ethanol on pregnancy and parturition itself. The purpose of this review is twofold. First we will consolidate and summarize data from both clinical and basic research that pertains to ethanol and parturition. These data will demonstrate that ethanol consumption during pregnancy results in both delayed as well as premature delivery depending upon the pattern of consumption and timing of exposure. With these data as a background, the second objective will be to present a theoretical case for prostaglandins as possible mediators of ethanol-induced effects on the onset of parturition.
Alcohol Drinking↗
Simultaneous analysis of multiple gene expression patterns as a function of development, injury or senescence.
Concurrent changes in expression of eight genes were examined following cryogenic rat brain injury. Cortical RNA levels were catalogued at time 0, and at 1 h and 1 week following injury. The genes include thymidine kinase (TK), c-fos, renin, myelin basic protein (MBP), proteolipid protein (PLP), glial fibrillary acidic protein (GFAP), insulin-like growth factor-1 (IGF-1), and somatostatin. All demonstrate increased expression following injury. Renin and c-fos exhibit detectable changes as early as 1 h post-injury.
Aging↗
The VISA score: an index of severity of symptoms in patients with jumper's knee (patellar tendinosis). Victorian Institute of Sport Tendon Study Group.
Symptoms of jumper's knee (patellar tendinosis) are not easily quantified and this may explain why there are no evidence-based guidelines for managing the condition. A simple, practical questionnaire-based index of severity would facilitate jumper's knee research and subsequently, clinical management. Thus we devised and tested the Victorian Institute of Sport Assessment (VISA) questionnaire. The brief questionnaire assesses (i) symptoms, (ii) simple tests of function and (iii) ability to play sport. Six of the eight questions are scored on a visual analogue scale from 0-10 with 10 representing optimal health. The maximal VISA score for an asymptomatic, fully performing individual is 100 points and the theoretical minimum is 0 points. We found the VISA scale to have excellent short-term test-retest, and inter-tester reliability (both, r>0.95) as well as good short-term (one week) stability (r=0.87). Mean (SD) of the VISA scores ranged from 95 (8) points in asymptomatic control subjects to 55 (12) points in patients who presented to a sports medicine clinic with jumper's knee and 22 (17) points in patients before surgery for chronic jumper's knee. Six- and twelve-months after surgery VISA scores returned to 49 (15) and 75 (17) points respectively, mirroring clinical recovery. We conclude that the VISA score is a reliable index of the severity of jumper's knee that has potential to aid clinicians and researchers.
Adult↗
Patellar tendon ultrasonography in asymptomatic active athletes reveals hypoechoic regions: a study of 320 tendons. Victorian Institute of Sport Tendon Study Group.
OBJECTIVE: To compare patellar tendon sonographic findings in active, currently asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: The Victorian Institute of Sport Tendon Study Group, an institutional elite athlete study group in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female athletes from the sports of basketball, cricket, netball, and Australian rules football. Forty athletes who had current symptoms of jumper's knee were excluded from analysis, leaving 320 subject tendons in athletes who were currently asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the dimensions of subject tendons and noted the presence or absence of hypoechoic regions and tendon calcification. Dimensions of hypoechoic regions were measured, and approximate cross-sectional areas were calculated. Chi-squared analysis was used to test the prevalence of hypoechoic regions in subjects and controls and men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions were more prevalent in athlete tendons (22%) than in controls (4%), in male subject tendons (30%) than in female subjects (14%), and in basketball players (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities were equally prevalent in men and women but more prevalent in basketball players (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were present in 35 of 250 (14%) patellar tendons in athletes who had never had anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas were present in asymptomatic patellar tendons of a proportion of elite athletes but rarely present in controls. This has implications for clinicians managing athletes with anterior knee pain.
Adult↗
Postoperative patellar tendon healing: an ultrasound study. VIS Tendon Study Group.
The patellar tendon donor site of 20 patients who underwent anterior cruciate ligament (ACL) reconstruction using the patellar tendon tissue as autograft was examined with high resolution 7.5 MHz ultrasound. The patients were randomly divided into four groups and studied at 3, 6, 9 or 12 months postoperatively. The size of the postoperative tendon defect was measured just distal to the lower pole of the patella. The size of the tendon defect diminished progressively from a mean of 109 mm2 at 3 months to a mean of 23 mm2 at 12 months. Increasing echogenicity was first noticed 12 months after tendon repair. Seven patients developed clinical features postoperatively of jumper's knee (patellar tendinosis). There were no ultrasound signs that differentiated these patients from asymptomatic patients. It is concluded that ultrasound provides objective evidence of patellar tendon healing after ACL reconstruction: the surgical defect diminished in size and became echogenic after a period of 12 months.
Adult↗
Patellar tendinopathy: some aspects of basic science and clinical management.
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Anti-Inflammatory Agents, Non-Steroidal↗
Subcutaneous rupture of the Achilles tendon.
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Achilles Tendon↗
Experimental tumour induction by SV40 transformed cells.
Although SV40 transforms cells from many species, transformed cells from species other than the Syrian hamster are rarely tumorigenic in immunocompetent animals. However, secondary manipulations of SV40-transformed cells can result in increased tumorigenicity. Some early observations on tumour induction by SV40 and transformed cells will be followed by a selected review of evidence suggesting that tumorigenicity of SV40-transformed cells involves serial mutations. An SV40-transformed rat cell model will be described to illustrate the changes in tumorigenic phenotype that can occur during tumour progression. This information will be used to propose that SV40 immortalization of cells (other than hamster cells) is only the first in a series of steps in the pathway toward tumorigenicity and that a complete understanding of the oncogenicity of SV40 will require definition of the secondary genetic events which complement SV40 immortalization to create the fully tumorigenic phenotype.
Animals↗
What is your diagnosis? Retinal dysplasia with concurrent developmental skeletal abnormalities in a Labrador retriever.
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Abnormalities, Multiple↗
Patients with multidrug-resistant tuberculosis with low CD4+ T cell counts have impaired Th1 responses.
Multidrug-resistant tuberculosis (MDRTB) has emerged as a challenging clinical problem in both HIV-infected and -uninfected individuals. In this study, immune responses from HIV-negative patients with MDRTB were compared with those of healthy purified protein derivative (PPD)-positive and PPD-negative individuals. These responses were characterized by measuring the proliferation and cytokine production from PBMCs stimulated in vitro with Mycobacterium tuberculosis, PPD, or mitogens. MDRTB patients with CD4 counts >500/microl stimulated in vitro with M. tuberculosis had similar immune responses (proliferation, IFN-gamma, and IL-2 production) as the PPD-positive and -negative controls. By contrast, MDRTB patients with CD4 counts <500/microl had markedly deficient immune responses to similar stimuli. In these patients, IFN-gamma production could be restored by adding IL-12 to the in vitro cultures. IL-12 also caused a striking increase in the amount of IFN-gamma produced from PBMCs of both PPD-positive and -negative controls. The role of endogenous IL-12 production was also studied. Addition of anti-IL-12 to cultures resulted in a two- to eightfold decrease in IFN-gamma production in response to PHA stimulation. Inhibition of IFN-gamma was also observed when cells were stimulated by M. tuberculosis and PPD. Using Staphylococcus aureus Cowan strain as a mitogenic stimulus, IL-12 p70 was produced in similar amounts in all groups tested. TNF-alpha production was also assessed from cells stimulated by M. tuberculosis. Addition of IL-12 to the cultures did not cause a significant enhancement of TNF-alpha production. Last, production of IL-10 and IL-4 in response to M. tuberculosis and PHA, respectively, was not significantly different among all groups tested. These results suggest that patients with MDRTB tuberculosis with CD4 T cell counts <500/microl have impaired IFN-gamma and IL-2 responses and might benefit by adjunctive IL-12 therapy.
CD4 Lymphocyte Count↗