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Biomedical subjects

M Collins

Publications and source records attributed to M Collins.

At least 91 records · Page 5Linked to original sources

Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation.

BACKGROUND: Ticlopidine has been shown to reduce the incidence of stent thrombosis compared with warfarin, but it may cause serious hematological side effects. Clopidogrel, a new thienopyridine derivative, may be a safe alternative to ticlopidine. The aim of this study was to compare the safety and efficacy of clopidogrel and aspirin with those of ticlopidine and aspirin in patients undergoing coronary stent implantation. METHODS AND RESULTS: The population of this study consisted of 2 groups: patients who underwent coronary stenting and were treated with ticlopidine and aspirin (TA group, n=1406), and patients who underwent coronary stenting followed by treatment with clopidogrel and aspirin (CA group, n=283). At 1-month follow-up, there was no difference in stent thrombosis (1.5% versus 1.4%, P=1.0) or major adverse cardiac events (3.1% versus 2.4%, P=0. 85) between the TA and CA groups, respectively. The probability of any side effect (neutropenia, diarrhea, rash) was significantly higher in the TA group (10.6% versus 5.3%, P=0.006; relative risk, 0. 53; CI, 0.32 to 0.86). CONCLUSIONS: These data suggest that clopidogrel may be an effective pharmacological regimen after coronary stent implantation. Furthermore, the simpler dosing regimen, the absence of neutropenia, and the lower frequency of other side effects make it a safe alternative to ticlopidine.

Aged↗

Does the presence of a tracheoesophageal fistula predict the outcome of laryngeal cleft repair?

OBJECTIVE: To determine if the presence of a tracheo-esophageal fistula (TEF) alters outcome following laryngeal cleft repair. DESIGN: A retrospective review of patients diagnosed and treated for laryngeal clefts, with a minimum follow-up period of 1 year. SETTING: An academic tertiary care children's hospital. PATIENTS: Twenty-five pediatric patients diagnosed and surgically treated for laryngeal cleft. MAIN OUTCOME MEASURES: Each chart was reviewed to determine if patients with a laryngeal cleft had been diagnosed with TEF and had undergone a surgical TEF repair procedure. The success of the surgery was evaluated based on the resolution of symptoms and the endoscopic evaluation of the repair site. RESULTS: Twenty-five patients were reviewed for study purposes. Fourteen had a history of TEF repair and 11, no history of TEF. All 25 patients underwent surgical repair of the laryngeal cleft. Twelve of the 14 patients with a history of TEF repair experienced a breakdown of the laryngeal cleft repair. Only 1 of the 11 patients with no history of TEF experienced such a breakdown. In 8 of 9 patients with a laryngotracheoesophageal type I cleft, surgical repair was not successful. CONCLUSIONS: In our series, patients with laryngeal clefts who also had a history of TEF had a much higher incidence of breakdown of cleft repair compared with patients with no history of TEF. This finding is not conclusive and requires further investigation. The failure of cleft repair correlated with the severity of the cleft. The importance of these associations may lead to enhanced surgical planning and realistic preoperative family expectations.

Abnormalities, Multiple↗

Differences in semantic category priming in the left and right cerebral hemispheres under automatic and controlled processing conditions.

The contribution of each cerebral hemisphere to the generation of semantic category meanings at automatic and strategic levels of processing was investigated in a priming experiment where prime and target words were independently projected to the left or right visual fields (LVF or RVF). Non-associated category exemplars were employed as related pairs in a lexical decision task and presented in two experimental conditions. The first condition was designed to elicit automatic processing, so related pairs comprised 20% of the positive set, stimulus pairs were temporally separated by a stimulus onset asynchrony (SOA) of 250 ms, and there was no allusion to the presence of related pairs in the instructions to subjects. The second condition, designed to invoke controlled processing, incorporated a relatedness proportion of 50%, stimulus pairs separated by an SOA of 750 ms, and instructions which informed subjects of the presence and use of category exemplar pairs in the stimulus set. In the first condition, a prime directed to either visual field facilitated responses to categorically related targets subsequently projected to the RVF, while in the second condition a prime directed to either visual field facilitated responses to related targets projected to the LVF. The facilitation effects obtained in both conditions appeared to reflect automatic processes, while strategic processes were invoked in the left, but not the right hemisphere in the second condition. The results suggest that both hemispheres have automatic access to semantic category meanings, although the timecourse of activation of semantic category meanings is slower in the right hemisphere than in the left.

Adult↗

A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis.

PURPOSE: The mechanisms of venous thrombogenesis have been studied by using animal models and cells in culture. The results from these systems may not, however, be relevant to the human condition. The aim of this study was to develop a method by which thrombus could be safely produced in a human vein in vivo. The model that was developed was used as a means of studying the changes in soluble adhesion molecule expression in human venous thrombogenesis. METHODS: An autologous thrombin extract was used to generate experimental thrombi in the disconnected portion of the long saphenous veins of 30 patients who were undergoing routine bilateral varicose vein surgery. The contralateral vein was perfused with thrombin extract diluent buffer to act as the control. The concentration of soluble P-, E- and L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 were measured by means of specific enzyme-linked immunosorbent assays in samples of blood taken from veins in which thrombus had formed and in contralateral control veins. RESULTS: Thrombosis invariably formed when at least 100 IU of thrombin activity was administered. Thrombus formation was independent of the time that the thrombin extract was allowed to remain within the emptied vessel. Thrombosis never developed in control vessels that were similarly treated with the buffer used to dilute the thrombin extract. Experimental thrombi were composed mainly of red cells, with layers of fibrin next to platelet and leukocyte packages. These findings are similar to those observed in samples of established human venous thrombi. There were small but significantly higher levels of the adhesion molecules, soluble P-selectin, and vascular cell adhesion molecule-1 in blood taken from veins in which experimental thrombi had formed, compared with controls (P =.015 and.007, respectively; Wilcoxon signed rank test). Serum levels of soluble L-selectin, E-selectin, and ICAM-1 were not affected by thrombosis. CONCLUSION: This model is safe and reproducible. It produces thrombi with a morphology similar to that described for established human deep venous thrombi. The model may be appropriate for the study of the early changes that occur during human venous thrombogenesis and may also be of value in testing the efficacy of novel antithrombotic agents.

Cell Adhesion Molecules↗

Assessment of regional wall motion abnormalities with real-time 3-dimensional echocardiography.

Accurate characterization of regional wall motion abnormalities requires a thorough evaluation of the entire left ventricle (LV). Although 2-dimensional echocardiography is frequently used for this purpose, the inability of tomographic techniques to record the complete endocardial surface is a limitation. Three-dimensional echocardiography, with real-time volumetric imaging, has the potential to overcome this limitation by capturing the entire volume of the LV and displaying it in a cineloop mode. The purpose of this study was to assess the feasibility of using real-time 3-dimensional (RT3D) echocardiography to detect regional wall motion abnormalities in patients with abnormal LV function and to develop a scheme for the systematic evaluation of wall motion by using the 3-dimensional data set. Twenty-six patients with high-quality 2-dimensional echo images and at least 1 regional wall motion abnormality were examined with RT3D echocardiography. For 2-dimensional echocardiography, wall motion was analyzed with a 16-segment model and graded on a 4-point scale from normal (1) to dyskinetic (4), from which a wall motion score index was calculated. Individual segments were then grouped into regions (anterior, inferoposterior, lateral, and apical) and the number of regional wall motion abnormalities was determined. The RT3D echocardiogram was recorded as a volumetric, pyramid-shaped data set that contained the entire LV. Digital images, consisting of a single cardiac cycle cineloop, were analyzed off-line with a computerized display of the apical projection. Two intersecting orthogonal apical projections were simultaneously displayed in cineloop mode, each independently tilted to optimize orientation and endocardial definition. The 2 planes were then slowly rotated about the major axis to visualize the entire LV endocardium. Wall motion was then graded in 6 equally spaced views, separated by 30 degrees, yielding 36 segments per patient. A higher percentage of segments were visualized with 2-dimensional versus RT3D echocardiography (97% vs 83%, respectively, P <.001). With the use of the 2-dimensional echocardiographic results as the standard, RT3D echocardiography detected 55 (96%) of 57 regional wall motion abnormalities. Analysis of the RT3D echocardiograms resulted in 3 false-negative and 5 false-positive findings. The total number of regional wall motion abnormalities was correctly classified by RT3D echocardiography in 19 (73%) of 26 patients. RT3D echocardiography detected 11 of 13 anterior, 19 of 20 inferoposterior, 9 of 9 lateral, and 15 of 15 apical wall motion abnormalities. An excellent correlation was found between the 2 techniques for assessment of the regional wall motion score index (r = 0.89, P <.001). This initial clinical study demonstrates the feasibility and potential advantages of RT3D echocardiography for the assessment of regional LV function. Compared with 2-dimensional echocardiography, this new method permits recording of the entire LV in a single beat, allowing the extent and location of the regional wall motion abnormalities to be determined.

Cardiomyopathy, Dilated↗

Acute hepatitis B infection in England and Wales: 1985-96.

Confirmed acute hepatitis B infections are reported to the Public Health Laboratory Service Communicable Disease Surveillance Centre by laboratories in England and Wales. These reports have been used to monitor trends in the incidence of hepatitis B virus (HBV) infection over time, and between exposure categories and age groups. Between 1985 and 1996 a total of 9252 cases of acute HBV infection were reported; the number of reports fell from 1761 in 1985 to 581 in 1996. Most infections were reported in adults aged 15-44 years [n = 7365 (80%)], and infections were more commonly reported in males [n = 6490 (70%)] than females [n = 2658 (29%)]. The probable means of acquisition was known for just over half of all adult cases [4827/8956 (54%)]. Injecting drug use was the most common exposure [n = 1901 (21%)], followed by sex between men and women [n = 1140 (13%)] and sex between men [n = 1025 (11%)]. The number of infections in injecting drug users fell in the late 1980s, but increased again from 1991 onwards. In children aged under 15 years, infections acquired by mother to baby transmission accounted for 35/170 (21%) of the total. Surveillance indicates that the incidence of acute hepatitis B infection fell in the late 1980s, probably reflecting changed behaviour in injecting drug users. An increase in the number of infections in injecting drug users since 1993 may indicate ongoing transmission that has not been contained by the introduction of needle exchange schemes or by selective vaccination.

Acute Disease↗

Cerebral responses to pain in patients suffering acute post-dental extraction pain measured by positron emission tomography (PET).

Previous studies with normal volunteers have demonstrated distributed cortical responses to experimental heat pain within a network of structures. The network includes the insula, anterior cingulate, prefrontal, inferior parietal and somatosensory cortices. Patients suffering from chronic nociceptive pain following rheumatoid arthritis (RA) have shown damped central responses to experimental heat pain applied to the back of the right hand. In this study of patients with acute, left-sided, post-molar-extraction (surgical) pain, we assessed the cortical responses to experimental heat pain, applied to the back of the right hand, using positron emission tomography (PET), and compared the responses with a previously reported control group and the RA group. In response to the experimental heat pain, the surgical group indicated significantly increased regional cerebral blood flow in the prefrontal cortex [Brodman's area (BA) 44] ipsilateral to the heat stimulus. Contralateral increases were detected in the putamen and transverse temporal gyrus (BA 40/41/42) with bilateral increases in the insular cortex. Compared to the control and RA group, there were significantly reduced responses in the anterior cingulate (BA 24), pre-frontal medial, and orbito-frontal (BA 9/10/32/47) cortices. These results suggest that relatively discrete regions of the cerebral cortex are responsible for acute nociceptive processing during an acute inflammatory episode. The reduced frontal and anterior cingulate responses to the experimental heat pain (applied to the right hand) during acute inflammatory pain (left jaw) illustrates cortical modulation of nociceptive processing that may be related to non-somatotopic, bilateral, nociceptive inputs to these areas. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

Retrovirus targeting by tropism restriction to melanoma cells.

Targeted vectors will be necessary for many gene therapy applications. To target retroviruses to melanomas, we fused a single-chain variable fragment antibody (scFv) directed against the surface glycoprotein high-molecular-weight melanoma-associated antigen (HMW-MAA) to the amphotropic murine leukemia virus envelope. A proline-rich hinge and matrix metalloprotease (MMP) cleavage site linked the two proteins. The modified viruses bound only to HMW-MAA-expressing cells, as inclusion of the proline-rich hinge prevented viral binding to the amphotropic viral receptor. Following attachment to HMW-MAA, MMP cleavage of the envelope at the melanoma cell surface removed the scFv and proline-rich hinge, allowing infection. Complexing of targeted retroviruses with 2, 3-dioleoyloxy-N-[2(spermine-carboxamido)ethyl]N, N-dimethyl-1-propanaminium trifluoroacetate-dioleoyl phosphatidylethanolamine liposomes greatly increased their efficiency without affecting their target cell specificity. In a cell mixture, 40% of HMW-MAA-positive cells but less than 0.01% of HMW-MAA-negative cells were infected. This approach can therefore produce efficient, targeted retroviruses suitable for in vivo gene delivery and should allow specific gene delivery to many human cell types by inclusion of different scFv and protease combinations.

Antibodies, Neoplasm↗

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators.

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Brain Damage, Chronic↗

Changes in the levels of soluble adhesion molecules and coagulation factors in patients with deep vein thrombosis.

Current biochemical markers of thrombosis, such as d-dimer, are of little value in demonstrating the presence of thrombus postoperatively, as their levels are elevated by surgery. Thrombosis involves adhesive interactions between the endothelium, platelets and leukocytes. The aim of the study was to determine which of a panel of haemostatic and adhesion factors are altered by the presence of thrombus, but not by surgery. These factors were measured in 20 patients with established spontaneous DVTs, 13 patients having hip replacement surgery and 28 control patients. Circulating levels of P-selectin, VCAM-1 and tissue factor were found to be increased when thrombus was present (p <0.018, p <0.0001, p <0.0028 respectively), but were not altered by surgery. The significance of these circulating factors in venous thrombosis remains to be established, but it is conceivable that they are the product of increased leukocyte trafficking and activity. Assay of VCAM-1, in particular, may be of use in the early detection of venous thrombi in postoperative patients.

Adult↗

Male genitourinary cancer sexuality questionnaire.

In recent years the focus of cancer nursing care has expanded to include not only survival issues, but also quality of life. Sexuality is a significant aspect of quality of life. The purposes of this study were to describe patient-identified sexuality information needs, and the preferred method and setting for receiving this information. The results provide nurses with a baseline to structure teaching sessions to best meet the needs of this population. In recent years the focus of cancer nursing care has expanded to include not only survival issues, but also quality of life. Sexuality is a significant aspect of quality of life acknowledged by the American Nurses Association and the Oncology Nursing Society (1979) as a designated aspect of nursing care since 1979. Fonesca describes sexuality as the quality of being human (Hughes, 1996). As an expression of one's self physically, socially, and psychologically, sexuality involves more than sexual activity. It is communicated in ways that include bodily movements, interactions with others in everyday encounters, and expressions of the deepest feelings of love (Fonesca, 1970). Sexuality also includes one's intimate feelings of individuality and the need for emotional closeness with another person.

Adult↗

Tuberculin skin test screening practices among US colleges and universities.

CONTEXT: Concern about transmission of Mycobacterium tuberculosis on college campuses has prompted some schools to institute tuberculin skin test screening of students, but this screening has never been evaluated. OBJECTIVE: To describe tuberculin skin test screening practices and results of screening in colleges and universities in the United States. DESIGN AND SETTING: Self-administered mail and telephone questionnaire in November and December 1995 to a stratified random sample of US 2-year and 4-year colleges and universities. MAIN OUTCOME MEASURES: Type of tuberculin screening required; types of schools requiring screening; number and rate of students with positive skin test results and/or diagnosed as having tuberculosis. RESULTS: Of the 3148 US colleges and universities, 624 (78%) of 796 schools surveyed responded. Overall, 378 schools (61%) required tuberculin screening; it was required for all new students (US residents and international students) in 161 (26%) of 624 schools, all new international students but not new US residents in 53 (8%), and students in specific academic programs in 294 (47%). Required screening was more likely in 4-year vs 2-year schools, schools that belonged to the American College Health Association vs nonmember schools, schools with immunization requirements vs schools without, and schools with a student health clinic vs those without (P<.001 for all). Public and private schools were equally likely to require screening (64% vs 62%; P=.21). In the 378 schools with screening requirements, tine or multiple puncture tests were accepted in 95 (25%); test results were recorded in millimeters of induration in 95 (25%); and 100 (27%) reported collecting results in a centralized registry or database. Of the 168 (27%) of 624 schools accepting only Mantoux skin tests and reporting results for school years 1992-1993 through 1995-1996, 3.1% of the 348 368 students screened had positive skin test results (median percentage positive, 0.8%). International students had a significantly higher case rate for active tuberculosis than US residents (35.2 vs 1.1 per 100000 students screened). CONCLUSIONS: Widespread tuberculin screening of students yielded a low prevalence of skin test reactors and few tuberculosis cases. To optimize the use of limited public health resources, tuberculin screening should target students at high risk for infection.

Adolescent↗

Characterization of two distinct families of transcription factors that bind to the CCAAT box region of the human COL1A2 gene.

Both the mouse and human alpha2(I) procollagen promoters contain an inverted CCAAT box at -80, but only the human promoter contains an additional regulatory element, the collagen modulating element (CME), immediately downstream of the CCAAT box [Collins et al. (1997): Biochem J 322:199-206]. In this study, the transcription factors that bind to the G/CBE and CME within the human promoter were characterized in SVWI-38 and CT-1 nuclear extracts. Two distinct proteins bind to the CME, and both were identified as heat-labile factors that were sensitive to high ionic strengths and required Zn2+ for DNA-binding activity. These proteins had Stokes radii of 4.12 and 3.15 nm, sedimentation coefficients of 3.9 and 3.2 S and native molecular weights of 66 and 41 kDa, respectively. On the basis of biochemical and DNA-binding properties, the CME binding proteins are probably novel factors involved in the regulation of the human alpha2(I) procollagen gene. By contrast, the G/CBE binding proteins were more resistant to heat, ionic strength, and divalent metal ion chelators, demonstrating that the G/CBE and CME binding proteins had distinct DNA-binding properties. The above properties suggest that this factor is a member of the previously characterized family of CCAAT box-binding factors, CBF, NF-Y, CP-1 and alpha-CP1. Taken together, these physicochemical properties of the COL1A2 CCAAT box and CME-binding proteins demonstrated that they were distinct unrelated transcription factors. These results also suggest that there is a distinct difference in the DNA-binding activity between the equivalent region of the mouse and human alpha2(I) procollagen promoters.

Animals↗