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Biomedical subjects

C Green

Publications and source records attributed to C Green.

At least 145 records · Page 8Linked to original sources

The Adolescents Training and Learning to Avoid Steroids (ATLAS) prevention program. Background and results of a model intervention.

OBJECTIVE: To develop and test a school-based intervention to prevent anabolic androgenic steroid use among high-risk adolescent athletes. DESIGN: Nonrandom controlled trial. SETTING: Two urban high schools. PARTICIPANTS: Fifty-six adolescent football players at the experimental school and 24 players at the control school. INTERVENTION: Eight weekly, 1-hour classroom sessions delivered by the coach and adolescent team leaders, and eight weight-room sessions delivered by research staff. The intervention addressed sports nutrition and strength training as alternatives to steroid use, drug refusal role play, and antisteroid media campaigns. OUTCOME MEASURES: A preintervention and postintervention questionnaire that assessed attitudes toward and intent to use steroids and other drugs; knowledge of drug effects; and diet, exercise, and related constructs. RESULTS: Compared with controls, experimental subjects were significantly less interested in trying steroids after the intervention, were less likely to want to use them even if their friends used them, were less likely to believe steroid use was a good idea, believed steroids were more dangerous, had better knowledge of alternatives to steroid use, had improved body image, increased their knowledge of diet supplements, and had less belief in these supplements as beneficial. CONCLUSIONS: Significant beneficial effects were found despite the sample size, suggesting that the effects of the intervention was large. This outcome trial demonstrates an effective anabolic androgenic steroid prevention program for adolescent athletes, and the potential of team-based interventions to enhance adolescents' health.

Adolescent↗

Cytochrome P450 species involved in the metabolism of quinoline.

Quinoline is a hepatocarcinogen in rats and mice and a well-known mutagen in bacteria after incubation with rat liver microsomes. The specific cytochrome P450 enzymes involved in quinoline metabolism in human and rat liver microsomes were determined using cDNA-expressed cytochrome P450s, correlations with specific cytochrome P450-linked monooxygenase activities in human liver microsomes and inhibition by specific inhibitors and antibodies. CYP2A6 is the principal cytochrome P450 involved in the formation of quinoline-1-oxide in human liver microsomes (correlation coefficient r = 0.95), but is formed in only minute quantities in rat liver microsomes. CYP2E1 is the principal cytochrome P450 involved in the formation of 3-hydroxyquinoline (r = 0.93) in human liver microsomes and is involved in the formation in rat liver microsomes. A high correlation coefficient (r = 0.91) between CYP2A6 activity and quinoline-5,6-diol formation in human liver microsomes was observed, but this most likely reflects the involvement of CYP2A6 in the formation of quinoline-5,6-epoxide, from which the quinoline-5,6-diol is formed, as conversion of quinoline-5,6-epoxide to quinoline-5,6-diol on incubation of the epoxide with CYP2A6 could not be demonstrated. A cDNA-expressed human microsomal epoxide hydrolase, however, efficiently converted the epoxide to the diol and the microsomal epoxide inhibitor cyclohexene oxide inhibited quinoline-5,6-diol formation in rat liver microsomes. A preliminary kinetic analysis of quinoline metabolism in human liver microsomes was carried out and Eadie-Hofstee plots indicate that the formation of quinoline-5,6-diol is monophasic, while that of quinoline-1-oxide and 3-hydroxyquinoline is biphasic.

Animals↗

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

Arteries↗

The effect of topically applied corticosteroid on irritant and allergic patch test reactions.

The purpose of the study was to assess the effect of topical corticosteroid on the patch test response in patients with known positive allergens and also to study any effect on the irritant response. In Study 1, 10 patients with known positive allergens had their backs pre-treated 2 x daily for 3 days with either betamethasone dipropionate 0.05% or the equivalent ointment base. On day 4, previous known allergens and dilutions of sodium lauryl sulfate (5% and 10%) as an irritant were applied to each side of the back. In Study 2 (4 patients), a 1:4 dilution of betamethasone dipropionate was substituted for the full-strength preparation. Betamethasone dipropionate 0.05% caused total or partial suppression of the allergic reaction in 8 of 10 cases. The 1:4 dilution caused partial suppression in 3 cases. The irritant reaction was totally suppressed by betamethasone dipropionate in 1 of 10 cases and partially suppressed in 7 of 10. The 1:4 dilution decreased the intensity of the irritant reaction in 3 of 4 cases. The relevance of these results to clinical practice is discussed.

Administration, Topical↗

Chronic pelvic pain and gynecological symptoms in women with irritable bowel syndrome.

Chronic pelvic pain and irritable bowel syndrome are common disorders, yet very little is known about their comorbidity. As part of an epidemiological study of patients with irritable bowel syndrome or irritable bowel disease we inquired about a history of chronic pelvic pain and related gynecological problems, and hypothesized that distress associated with either of these conditions was additive in women with both syndromes. A medically trained interviewer evaluated a sequential sample of 60 women with irritable bowel syndrome and 26 women with inflammatory bowel disease in an urban gastroenterology clinic using the National Institute of Mental Health Diagnostic Interview Schedule, the Briere Child Maltreatment Interview (emotional, physical and sexual abuse), and a structured interview to elicit a lifetime history of chronic pelvic pain that was distinct from the history of bowel distress. Chronic pelvic pain was reported in 21 (35.0%) of the irritable bowel syndrome patients vs. 4 (13.8%) of the inflammatory bowel disease group (p < 0.05). Compared to women with irritable bowel syndrome alone, those with both irritable bowel syndrome and chronic pelvic pain were significantly more likely to have a lifetime history of dysthymic disorder, current and lifetime panic disorder, somatization disorder, childhood sexual abuse and hysterectomy. Logistic regression showed that mean number of somatization symptoms was the best predictor of a history of both irritable bowel syndrome and chronic pelvic pain compared either to inflammatory bowel disease or irritable bowel syndrome alone. Many women with irritable bowel syndrome may have a history of chronic pelvic pain as well. The high rates of psychopathology associated with irritable bowel syndrome and chronic pelvic pain independently are even higher in women with both syndromes, and women who present with either irritable bowel syndrome or chronic pelvic pain should probably be evaluated for both disorders.

Adult↗

(+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 in human liver microsomes.

(+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) was oxidized by human liver microsomes to produce the S-oxide as a sole metabolite. Indirect evidence suggested that the S-oxidation was catalyzed by cytochrome P450 (CYP). Eadie-Hofstee plots showed biphasic pattern, suggesting that at least two enzymes were involved in the S-oxidation in human liver microsomes. Kinetic parameters of the S-oxidase with high-affinity showed Km and Vmax values of 20.9 +/- 4.4 microM and 0.111 +/- 0.051 nmol/min/mg microsomal protein, respectively. The S-oxidase activity was inhibited by coumarin and anti-CYP2A antibody. Among the contents of forms of CYP 20 samples of human liver microsomes, the content of CYP2A6 correlated with S-oxidase activity measured with 50 microM SM-12502 (r = .808, P < .0005). A close correlation (r = .908, P < .0001) was observed between activities of SM-12502 S-oxidase and coumarin 7-hydroxylase. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP2A6 metabolized SM-12502 to the S-oxide efficiently. The results indicate that CYP2A6 isozyme is a major form of CYP responsible for the S-oxidation of SM-12502 in human liver microsomes. Thus, SM-12502 will be a useful tool in further research to analyze a human genetic polymorphism of CYP2A6.

Animals↗

Liquefaction of cortical tissue in diabetic and galactosemic rat lenses defined by confocal laser scanning microscopy.

PURPOSE: To investigate whether a histologic link exists between osmotic fiber cell swelling and cortical tissue liquefaction in experimentally induced diabetic and galactosemic cataractogenesis of the rat lens. METHODS: Confocal laser scanning microscopy, in conjunction with specific membrane labels and correlative transmission electron microscopy, was used to image large cortical areas with precise definition of the individual cells. RESULTS: In both cataract models, tissue liquefaction--defined as the disintegration of tissue and the appearance of large fluid-filled spaces--typically was limited to a discrete zone in the lens cortex. The borders of the liquefaction zone were characterized by transitions between normal-appearing cells and swollen cells, which gained in size as plasma membranes ruptured and cytoplasmic contents fused and ultimately burst, thereby contributing to the formation of large fluid-filled spaces. During cataractogenesis, before tissue liquefaction became evident, selected fiber cells appeared swollen and accumulated specifically in the zone destined for tissue liquefaction. With increasing duration of diabetes or galactosemia, swollen fiber cells in this zone became more frequent and enlarged, resulting first in tissue disorder and then in tissue disintegration and the formation of large fluid-filled spaces. CONCLUSIONS: New imaging protocols strongly support a direct involvement of lens fiber cell swelling in the liquefaction of cortical tissue. The appearance of swollen fiber cells in the lens cortex, therefore, can be used as an early indicator of the histopathology of sugar cataractogenesis.

Animals↗

Plasma exchange therapy for solar urticaria.

We report two cases of severe idiopathic solar urticaria treated with plasma exchange therapy. Previous treatment which included antihistamines and, in one patient, desensitization with psoralens and ultraviolet A (PUVA) and narrowband ultraviolet B phototherapy produced only partial benefit. The effect of plasma exchange therapy was assessed using monochromator phototesting and intradermal injection of in vitro irradiated serum. One patient responded but relapsed within 2 weeks. We have failed to demonstrate a lasting benefit from plasma exchange therapy (PExT) in the treatment of two patients with idiopathic solar urticaria.

Adult↗

Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes.

BACKGROUND: The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy. METHODS AND RESULTS: Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median aPTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P < .0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P < .0002). Modified antithrombin III decreased over time (P < .002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P < .001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C. CONCLUSIONS: This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.

Aged↗

Immunoglobulin deposits in synovial membrane and cartilage and phenotype analysis of chondrocyte antigens in sheep infected with the visna retrovirus.

Synovial membranes and cartilage slices from sheep infected with the maedi-visna retrovirus were examined for immunoglobulin deposits by immunohistology. Granular deposits of IgM and IgG were observed in the synovial membranes and upper layers of cartilage from about 40% of virus-infected sheep. These deposits were present in animals with subclinical joint disease, as well as those affected clinically. No significant deposits were found in the synovial membrane or cartilage from normal sheep. Infected animals tended to have reduced cartilage proteoglycan staining. Altered expression of MHC class II, CD1 and adhesion molecules by chondrocytes in cartilage from infected sheep with clinical or subclinical synovitis was observed suggesting that in vivo cell activation is an early event in cartilage degradation in these infections. Exogenously derived antiviral antibodies exhibited molecular mimicry towards chondrocyte antigens, but no in vivo evidence for cross-reactivity was observed. The results showed that IgM and IgG deposits, putatively containing either virus/antivirus immune complexes or autoantibodies were formed in the joints of sheep with clinical or subclinical synovitis. These immune deposits may initiate and perpetuate chronic inflammation with concomitant activation of chondrocytes leading to pannus formation and cartilage destruction.

Animals↗

Transplantation of keratinocytes in the treatment of wounds.

BACKGROUND: Keratinocyte grafting can be used to treat acute traumatic and chronic non-healing wounds. The keratinocyte sheets are fragile and clinical "take" is difficult to assess, especially as activated keratinocytes secrete many growth factors, which have effects on wound healing apart from take. We have developed animal models of grafting that allow us to examine factors influencing autologous keratinocyte graft take. Results show clearly that pretreatment of the wound bed with viable dermis greatly increases the take of keratinocyte grafts. DATA SOURCES: International literature. CONCLUSIONS: As a greater understanding of the complex interactions of cell and matrix evolve, so will potential therapeutic maneuvers, not just in the field of cultured keratinocyte grafts, but clearly in that of benign tumors, for example, keloids, and that of oncology. There is now overwhelming evidence of the requirement for a dermal substitute for cultured keratinocyte autografts, and the sheet complexity of the situation demands that this should approximate live human dermis as closely as possible. The stumbling blocks relate to avoiding the risks of viral transmission, tissue matching of host and donor, providing early epithelial cover, and improving delivery systems for fragile keratinocyte grafts.

Animals↗

Changes in lens connexin expression lead to increased gap junctional voltage dependence and conductance.

The differentiation of mouse lens epithelial cells into fiber cells is a useful model for studying the changes of the electrical properties of gap junction (cell-to-cell) channels that are induced by an alteration in connexin expression patterns. In this model, cuboidal lens epithelial cells differentiate into elongated fiber cells, and the expression of connexin43 (Cx43) in the epithelial cells is replaced with the production of high levels of Cx50 and Cx46 in the fiber cells. We now report a new procedure to isolate mouse lens fiber cell pairs suitable for double whole cell patch-clamp analysis. Analysis was also performed for fiberlike cell pairs differentiated from epithelial cells in culture. Voltage dependence and unitary conductance of fiber cell gap junction channels were determined and compared with the corresponding values previously measured for the channels joining lens epithelial cells and for lens connexin channels formed in Xenopus oocyte pairs. Our results support a differentiation-induced shift toward stronger gap junctional voltage dependence and larger unitary conductances in the fiber cells. Our data further reflect a balanced functional contribution of Cx50 and Cx46 in the fiber cell-to-cell channels rather than a predominance of a single connexin.

Animals↗

MELAS syndrome: imaging and proton MR spectroscopic findings.

PURPOSE: To evaluate imaging findings in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, strokes) syndrome for the presence and location of infarctions and the presence of lactate. METHODS: Eight patients were studied with MR (n = 8) and CT (n = 2). One patient underwent single-photon emission CT with technetium 99m hexamethyl-propyleneamine oxime and one patient had conventional catheter angiography. One fixed brain was studied with MR imaging. Five patients underwent single volume proton MR spectroscopy. Imaging studies were evaluated for atrophy, edema, and infarctions. Proton MR spectroscopy was visually analyzed for presence or absence of lactate. RESULTS: One patient showed a cerebral infarction, and later a second distant infarction developed. One patient showed a transient area of cortical edema. Two patients had small nonspecific periventricular white matter abnormalities and one patient had diffuse white matter hyperintensities. Two patients had nonspecific MR abnormalities (probably age-related changes), and two had normal MR findings. None had basal ganglia involvement. Proton MR spectroscopy showed presence of lactate in one case with transient cortical edema; in two cases with nonspecific (probably age-related) brain findings; and in two patients with normal MR findings. CONCLUSIONS: Patients with MELAS have a variety of MR findings. The fact that proton MR spectroscopy showed lactate in all five cases studied, regardless of MR findings, indicates that proton MR spectroscopy may be more sensitive in the detection of MELAS-associated abnormalities than MR imaging.

Adolescent↗

Proton MR spectroscopy in patients with neurofibromatosis type 1: evaluation of hamartomas and clinical correlation.

PURPOSE: To use proton MR spectroscopy in patients with neurofibromatosis type 1 to determine: (a) the spectroscopic characteristics of hamartomas and compare them with that of gliomas; (b) whether differences exist between patients with and without learning disabilities; and (c) spectroscopic patterns in normal-appearing brain (by MR imaging) in patients with and without focal lesions. METHODS: Seventeen proton MR spectroscopy volumes were obtained in 10 patients with neurofibromatosis type 1 (including hamartomas, N = 7; normal-appearing brain, N = 10). Seven patients had learning disorders, and 3 were mentally normal. Ten healthy volunteers and 10 patients with pathologically proved gliomas (all grades) were also examined. N-Acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were calculated for all samples. RESULTS: (a) Hamartomas showed higher N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios than gliomas. Hamartomas showed N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios similar to those of healthy volunteers. (b) No significant differences in N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were found in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were similar for patients who had neurofibromatosis type 1 with and without focal hamartomas and in healthy volunteers. CONCLUSIONS: (a) Hamartomas have a proton MR spectroscopy pattern different from that of glioma and similar to that of normal brain. (b) As performed in this study, proton MR spectroscopy did not show significant differences in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) Patients who have neurofibromatosis type 1 with and without hamartomas seem to have normal intervening brain by proton MR spectroscopy when compared with healthy volunteers.

Adolescent↗