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Biomedical subjects

J Long

Publications and source records attributed to J Long.

At least 19 recordsLinked to original sources

Contaminants-induced oxidative damage on the carp Cyprinus carpio collected from the upper Yellow River, China.

The Yellow River, the second largest river in China, is the most important resource of water supply in North China. In the last 40 years, even in the upper Yellow River, with the development of industry and agriculture, more and more contaminants have been discharged into this river and greatly polluted the water. Although a routine chemical component analysis has been performed, little is known about the real toxic effects of the polluted water on organisms at environmental level. To explore whether the pollutants induced oxidative stress and damage to aquatic organisms, malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in hepatopancreas, kidney and intestine of the field-collected carp Cyprinus carpio from a mixed polluted (Lanzhou Region, LZR) and a relatively unpolluted (Liujiaxia Region, LJXR) sites of the upper Yellow River were measured. The results showed that when the values of LZR compared with those of LJXR, SOD and GST activities increased and GPx activity decreased significantly in all the three organs (P < 0.05-0.01); CAT activity decreased but MDA level increased significantly (P < 0.05-0.01) only in kidney and intestine. In conclusion, the results of this study suggest that the pollutants can induce obvious oxidative damage in the carp, and the SOD, GST and GPx might be better indicators for the oxidative damage in aquatic organisms.

Animals↗

On the role of energy barriers in determining contact angle hysteresis.

The thermodynamic model of contact angles on rough, heterogeneous surfaces developed by Long et al. [J. Long, M.N. Hyder, R.Y.M. Huang and P. Chen, Adv. Colloid Interface Sci. 118 (2005) 173] was employed to study the role of energy barriers in determining contact angle hysteresis. Major energy barriers corresponding to metastable states and minor energy barriers corresponding to secondary metastable states were defined. Distributions of major and/or minor energy barriers as a function of apparent contact angle for various surfaces were obtained. The reproducibility of contact angle measurement, the effect of vibrational energy on contact angle hysteresis and the "stick-slip" phenomenon were discussed. Quantitative relations between contact angles and vibrational energy were obtained. It was found that receding contact angles are normally poorly reproducible for hydrophilic surfaces, but for extremely hydrophobic surfaces, advancing contact angles may have a poor reproducibility. When the vibrational energy available to a system increases, the measured advancing contact angle will decrease while the receding angle will increase until both reach a common value: the system equilibrium angle. This finding not only agrees well with the experimental observations in system equilibrium contact angle measurements, but also lays a theoretical foundation for such measurements. A small vibrational energy may result in a "stick-slip" phenomenon.

Journal Article↗

Probing colloidal forces between a Si3N4 AFM tip and single nanoparticles of silica and alumina.

The atomic force microscope (AFM) has been used to measure surface forces between silicon nitride AFM tips and individual nanoparticles deposited on substrates in 10(-4) and 10(-2) M KCl solutions. Silica nanoparticles (10 nm diameter) were deposited on an alumina substrate and alumina particles (5 to 80 nm diameter) were deposited on a mica substrate using aqueous suspensions. Ionic concentrations and pH were used to manage attractive substrate-particle electrostatic forces. The AFM tip was located on deposited nanoparticles using an operator controlled offset to achieve stepwise tip movements. Nanoparticles were found to have a negligible effect on long-range tip-substrate interactions, however, the forces between the tip and nanoparticle were detectable at small separations. Exponentially increasing short-range repulsive forces, attributed to the hydration forces, were observed for silica nanoparticles. The effective range of hydration forces was found to be 2-3 nm with the decay length of 0.8-1.3 nm. These parameters are in a good agreement with the results reported for macroscopic surfaces of silica obtained using the surface force apparatus suggesting that hydration forces for the silica nanoparticles are similar to those for flat silica surfaces. Hydration forces were not observed for either alumina substrates or alumina nanoparticles in both 10(-4) M KCl solution at pH 6.5 and 10(-2) M KCl at pH 10.2. Instead, strong attractive forces between the silicon nitride tip and the alumina (nanoparticles and substrate) were observed.

Journal Article↗

AFM colloidal forces measured between microscopic probes and flat substrates in nanoparticle suspensions.

Colloidal forces between atomic force microscopy probes of 0.12 and 0.58 N/m spring constant and flat substrates in nanoparticle suspensions were measured. Silicon nitride tips and glass spheres with a diameter of 5 and 15 mum were used as the probes whereas mica and silicon wafer were used as substrates. Aqueous suspensions were made of 5-80 nm alumina and 10 nm silica particles. Oscillatory force profiles were obtained using atomic force microscope. This finding indicates that the nanoparticles remain to be stratified in the intervening liquid films between the probe and substrate during the force measurements. Such structural effects were manifested for systems featuring attractive and weak repulsive interactions of nanoparticles with the probe and substrate. Oscillation of the structural forces shows a periodicity close to the size of nanoparticles in the suspension. When the nanoparticles are oppositely charged to the probes, they tend to coat the probes and hinder probe-substrate contact.

Journal Article↗

p62 mutations, ubiquitin recognition and Paget's disease of bone.

Functional analyses of PDB (Paget's disease of bone)-associated mutants of the p62 [also known as SQSTM1 (sequestosome 1)] signalling adaptor protein represent an interesting paradigm for understanding not only the disease mechanism in this skeletal disorder, but also the critical determinants of ubiquitin recognition by an ubiquitin-binding protein. The 11 separate PDB mutations identified to date all affect the C-terminal region of p62 containing the UBA domain (ubiquitin-associated domain), a ubiquitin-binding element. All of these mutations have deleterious effects on ubiquitin binding by p62 in vitro, and there is evidence of an inverse relationship between ubiquitin-binding function and disease severity. The effects on ubiquitin-binding function of most of the mutations can be attributed to either reduced UBA domain stability, and/or the mutations affecting the presumed ubiquitin-binding interface of the UBA domain. However, a subset of the mutations are more difficult to rationalize; several of these affect sequences of p62 outside of the minimal ubiquitin-binding region, providing insights into non-UBA domain sequences within the host protein which mediate ubiquitin-binding affinity. The p62 mutations are presumed to result in activation of (osteoclast) NF-kappaB (nuclear factor kappaB) signalling. Understanding how loss of ubiquitin-binding function of p62 impacts on signal transduction events in osteoclasts will undoubtedly further our understanding of the disease mechanism in PDB at the molecular level.

Adaptor Proteins, Signal Transducing↗

The restoration of Loch Leven, Scotland, UK.

This paper reviews the progress made towards the restoration of Loch Leven, the largest lake in lowland Scotland, over the last 20 years. In particular, the importance of direct regulation and of setting water quality objectives and targets is examined. Various means of engaging with stakeholders and the general public are also considered. Success criteria and catchment management initiatives are described and briefly reviewed.

Conservation of Natural Resources↗

HIV infection among heroin users and area of residence.

The aim of this study was to develop a hypothesis to explain the link between HIV prevalence and area of residence. The study was conducted in two parts using two existing data sources. In Part 1, the bloodborne viral test status and test results of a sample of clients attending treatment in December 2001 in two areas of Dublin, an inner city area (Dublin 8) and a suburban area (Dublin 24), were extracted from the Bloodborne Viral Status Dataset created by Grogan. In Part 2 the characteristics of heroin users seeking treatment for the first time at treatment services in their respective areas of residence, Dublin 8 or Dublin 24, between 1997 and 2000 were examined, using data from the National Drug Treatment Reporting System. A higher proportion of heroin users in Dublin 8 had HIV and hepatitis C than did their counterparts in Dublin 24. The analysis suggests that heroin users in Dublin 8 were more likely both to have ever used cocaine and to have used heroin daily, than were those who lived in Dublin 24. Also, a higher proportion of injectors living in Dublin 8 used heroin and cocaine concurrently than did their counterparts in Dublin 24. In both samples, heroin users who lived in Dublin 8 were older than those who lived in Dublin 24. The findings led to a hypothesis:'The risk of acquiring HIV is associated with area of residence and may be linked to cocaine use.

Adolescent↗

High-dose chemotherapy and peripheral blood stem cell support in refractory gestational trophoblastic neoplasia.

We present retrospectively our experience in the use of high-dose chemotherapy and haematopoietic stem cell support (HSCS) for refractory gestational trophoblastic neoplasia (GTN) in the largest series so far reported. In all, 11 patients have been treated at three Trophoblast Centres between 1993 and 2004. The conditioning regimens comprised either Carbop-EC-T (carboplatin, etoposide, cyclophosphamide, paclitaxel and prednisolone) or CEM (carboplatin, etoposide and melphalan) or ICE (ifosfamide, carboplatin, etoposide). Two patients had complete human chorionic gonadotrophin responses, one for 4 and the other for 12 months. Three patients had partial tumour marker responses for 1-2 months. High-dose chemotherapy and HSCS for GTN is still unproven. Further studies are needed, perhaps in high-risk patients who fail their first salvage treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Thermodynamic modeling of contact angles on rough, heterogeneous surfaces.

Theoretical modelling for contact angle hysteresis carried out to date has been mostly limited to several idealized surface configurations, either rough or heterogeneous surfaces. This paper presents a preliminary study on the thermodynamics of contact angles on rough and heterogeneous surfaces by employing the principle of minimum free energy and the concept of liquid front. Based on a two-dimensional regular model surface, a set of relations were obtained, which correlate advancing, receding and system equilibrium contact angles to surface topography, roughness and heterogeneity. It was found that system equilibrium contact angles (theta(ES)) can be expressed as a function of surface roughness factor (delta) and the Cassie contact angle (theta(C)): costheta(ES) = deltacostheta(C). This expression can be reduced to the classical Wenzel equation.: theta(ES) = theta(W) for rough but homogeneous surfaces, and the classical Cassie equation theta(ES) = theta(C) for heterogeneous but smooth surfaces. A non-dimensional parameter called surface feature factor (omega) was proposed to classify surfaces into three categories (types): roughness-dominated, heterogeneity-dominated and mixed-rough-heterogeneous. The prediction of advancing and receding contact angles of a surface is dependent on which category the surface belongs to. The thermodynamic analysis of contact angle hysteresis was further extended from the regular model surface to irregular surfaces; consistent results were obtained. The current model not only agrees well with the models previously studied by other researchers for idealized surfaces, but also explores more possibilities to explain the reported experimental results/observations that most existing theories could not explain.

Colloids↗

Use of the emergency room in Elliot Lake, a rural community of Northern Ontario, Canada.

INTRODUCTION: There is ample documentation that use of hospital emergency facilities for reasons other than urgencies/emergencies results in clogged services in many urban centers. However, little has been published about similar misuse of emergency rooms/departments in rural and remote areas, where the situation is usually compounded by a scarcity of healthcare professionals. In Canada there is a shortage of physicians in rural and remote areas as a consequence of misdistribution (most physicians staying in southern urban centers after residence), and there is a chronic misuse of facilities meant for urgencies/emergencies to cope with primary healthcare needs. We address the problem in Elliot Lake, a rural Northern Ontario community of 12,000 people. The economy of Elliot Lake was based on uranium mining until the mid-1990s, when it drastically changed to become a center for affordable retirement and recreational tourism. As a consequence, at the present time the proportion of seniors in Elliot Lake doubles the Canadian average. Our objectives are to elucidate the demographics of emergency room (ER) clients and the effect of the elderly population; the nature of ER use; the perceived level of urgency of clients versus health professionals; and possible alternatives offered to non-urgent/emergency visits. This is the first study of the kind in Northern Ontario, a region the size of France. METHODS: The study, conducted in July 2001, used a prospective survey, completed by patients and attending clinicians at the time of a patient's presentation to the ER of St Joseph's General Hospital. This hospital is staffed by family physicians, a nurse practitioner, and registered nurses (RNs). The catchment area population (town plus surrounding areas) of the hospital is approximately 18,000 people. ER clients were interviewed verbally, and the attending health professionals responded to written questionnaires. Demographics were recorded (age, sex, employment and marital status), as was each client's reason for making an ER visit. Clients were asked if they had a family physician and if they had contacted him/her before visiting the ER, and if they would use another agency to address their health problem. Each client's, nurse's, and physician/nurse practitioner's perceived urgency level was recorded on a scale from 1 (non-urgent) to 5 (extremely urgent/life threatening). The attending physician/nurse practitioner and attending nurse were also asked to recommend appropriate alternatives, in their judgment, to each ER visit. RESULTS: Of a total of 1472 ER cases, 1096 (74.5%) verbal interviews with clients were conducted, as well as 1298 (88.2%) and 1013 (68.8%) questionnaires were completed respectively by attending nurses and physicians/nurse practitioner. The age of the clients was roughly proportional to their cohorts in the catchment area. Males and females were equally represented in the sample. Only 28.8% of the clients contacted their family physicians before visiting the ER, although 80.9% of them had a family physician. The reasons for visiting the ER are mostly typical of a primary care practice in Canada, and ER clients considered 19.4% of their visits non-urgent/non-emergency. In contrast, 45.2% of the physicians/nurse practitioner and 63.7% of the nurses considered the visits non-urgent/non-emergency. To reduce ER misuse, two-thirds of the recommendations by staff were to recruit more family physicians and nurse practitioners, and another one-fifth of the recommendations suggested the creation of a walk-in clinic. Other alternatives, such as the use of a variety of agencies available in town, were minimally recommended by healthcare professionals. CONCLUSION: The core of the problem identified by this research is that more physicians, nurse practitioners, and other health care professionals are needed in Elliot Lake to provide continuity of care. A new medical school is being created for the region, but the first family physicians from this initiative will only be available in 2012. In the meantime, healthcare professionals may need to take more preventive and educational measures to reduce ER misuse, and the use of other town's agencies, Telehealth, case-management of recurrent clients, and collaboration with local pharmacists need to be maximized. Further research is urgently needed into the effects on health outcomes in rural communities that may result from health services having to function beyond their capacity. Rural health clinicians, communities, researchers, and policy makers must work together to design, implement, and evaluate, both immediate and longer term solutions to the problems identified in this study.

Journal Article↗

Outcomes following childhood head injury: a population study.

OBJECTIVES: To identify outcomes following head injury (HI) among a population of children admitted to one hospital centre and to compare outcomes between different severity groups. METHODS: A postal follow up of children admitted with HI to one National Health Service Trust, between 1992 and 1998, was carried out. Children were aged 5-15 years at injury (mean 9.8), followed up at a mean of 2.2 years post-injury. Parents of 526 injured children (419 mild, 58 moderate, 49 severe) and 45 controls completed questionnaires. Outcomes were assessed using the King's Outcome Scale for Childhood Head Injury (KOSCHI). RESULTS: Frequent behavioural, emotional, memory, and attention problems were reported by one third of the severe group, one quarter of the moderate, and 10-18% of the mild. Personality change since HI was reported for 148 children (28%; 21% mild HI, 46% moderate, 69% severe). There was a significant relationship between injury severity and KOSCHI outcomes. Following the HI, 252 (48%) had moderate disability (43% mild HI, 64% moderate, 69% severe), while 270 (51%) made a good recovery (57% mild HI, 36% moderate, 22% severe). There was a significant association between social deprivation and poor outcome (p = 0.002). Only 30% (158) of children received hospital follow up after the HI. All children with severe disability received appropriate follow up, but 64% of children with moderate disability received none. No evidence was found to suggest a threshold of injury severity below which the risk of late sequelae could be safely discounted. CONCLUSIONS: Children admitted with mild HI may be at risk of poor outcomes, but often do not receive routine hospital follow up. A postal questionnaire combined with the KOSCHI to assess outcomes after HI may be used to identify children who would benefit from clinical assessment. Further research is needed to identify factors that place children with mild HI at risk of late morbidity.

Adolescent↗

Identification of a mutation associated with erythromycin resistance in Bordetella pertussis: implications for surveillance of antimicrobial resistance.

Erythromycin treatment failures and in vitro resistance of Bordetella pertussis have been reported on several occasions in the past few years, but the mechanism of resistance has not been described. One potential mechanism, genetic modification of the erythromycin-binding site on the 23S rRNA of the 50S ribosomal subunit, has been observed in other bacteria. To explore this possibility, we amplified the portion of the 23S rRNA gene encoding the central loop of domain V. DNA sequencing and restriction fragment length polymorphism of the PCR products showed that each of the four erythromycin-resistant B. pertussis strains tested contained an A-to-G transition mutation at position 2058 (Escherichia coli numbering) of the 23S rRNA gene. The mutation was not found in seven erythromycin-susceptible isolates tested. Two of the resistant isolates were heterozygous, containing at least one mutant copy and one wild-type copy of the 23S rRNA gene. These results indicate that erythromycin resistance in these strains is likely due to a mutation of the erythromycin-binding site in the 23S rRNA gene. Identification of the resistance mechanism will facilitate development of molecular susceptibility testing methods that can be used directly on clinical specimens in the absence of an isolate.

Anti-Bacterial Agents↗

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection.

BACKGROUND: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. OBJECTIVE: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. METHODS: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. RESULTS: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis. CONCLUSIONS: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

Cytomegalovirus↗

Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey.

OBJECTIVES: To determine the prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in entrants to Irish prisons and to examine risk factors for infection. DESIGN: Cross sectional, anonymous survey, with self completed risk factor questionnaire and oral fluid specimen for antibody testing. SETTING: Five of seven committal prisons in the Republic of Ireland. PARTICIPANTS: 607 of the 718 consecutive prison entrants from 6 April to 1 May 1999. MAIN OUTCOME MEASURES: Prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in prison entrants, and self reported risk factor status. RESULTS: Prevalence of antibodies to hepatitis B core antigen was 37/596 (6%; 95% confidence interval 4% to 9%), to hepatitis C virus was 130/596 (22%; 19% to 25%), and to HIV was 12/596 (2%; 1% to 4%). A third of the respondents had never previously been in prison; these had the lowest prevalence of antibodies to hepatitis B core antigen (4/197, 2%), to hepatitis C (6/197, 3%), and to HIV (0/197). In total 29% of respondents (173/593) reported ever injecting drugs, but only 7% (14/197) of those entering prison for the first time reported doing so compared with 40% (157/394) of those previously in prison. Use of injected drugs was the most important predictor of antibodies to hepatitis B core antigen and hepatitis C virus. CONCLUSIONS: Use of injected drugs and infection with hepatitis C virus are endemic in Irish prisons. A third of prison entrants were committed to prison for the first time. Only a small number of first time entrants were infected with one or more of the viruses. These findings confirm the need for increased infection control and harm reduction measures in Irish prisons.

Adolescent↗

Triggered electromyographic threshold for accuracy of thoracic pedicle screw placement in a porcine model.

STUDY DESIGN: A porcine model of thoracic pedicle screw insertion was used to determine the effect of screw position on triggered electromyographic response. OBJECTIVE: To develop a model of intraoperative detection of misplaced thoracic pedicle screws. SUMMARY OF BACKGROUND DATA: Triggered electromyographic stimulation has been a valuable aid in determining appropriate placement of lumbar pedicle screws. The use of pedicle screws is increasing in the thoracic spine. Misplaced thoracic pedicle screws may have significant implications if the spinal cord is injured. This study was an attempt to determine whether the established lumbar model can be used for thoracic pedicle screws. METHODS: Five 120- to 150-lb domestic pigs had 85 pedicle screws placed bilaterally in the thoracic spine at each level from T6 to T15. Screws were inserted entirely in the pedicle (Group A). After removal of the medial pedicle wall, the screws were reinserted in the pedicle with no neural contact (Group B). The screws were then placed with purposeful contact with the neural elements (Group C). The screws were stimulated, eliciting an electromyographic response in the intercostal muscles for each instrumented level. The type of response noted was classified as either primary (response from appropriate nerve root), secondary (response at different root) or no response (response at different root, no response at appropriate root). RESULTS: Two hundred fifty responses were recorded. A primary response was noted in 72% of recordings. There was a relatively consistent decrease in the triggered electromyographic response from Group A (mean 4.15 +/- 1.80 mA) to Group C (mean 3.02 +/- 2.53 mA) screws (P = 0.0003). There was little difference in the response obtained from Group A to Group B (mean 4.37 +/- 2.48 mA) screws (P > 0.05). When a primary response was recorded, the mean threshold electromyographic response recorded was significantly lower than recordings with secondary and no response recordings (P < 0.05). CONCLUSION: Even though there was a consistent decrease between the A and C screws that was more definitively separated when a primary response was elicited, it was not possible to determine a cutoff trigger electromyographic level that would consistently differentiate intraosseous from epidural pedicle screw placement. Furthermore, this method could not differentiate screws clearly in the pedicle from screws with medial pedicle wall breakthrough. A more direct method of spinal cord monitoring must be established to provide the surgeon with early warning of the potential of neural injury in the placement of thoracic pedicle screws.

Animals↗

Short-term sequelae of minor head injury (6 years experience of minor head injury clinic).

PURPOSE: It is known that post-concussive symptoms may persist after mild head injury. However, the majority of those patients are denied follow-up or support. A minor head injury clinic was thus established in North Staffordshire Hospital in 1993 to address these problems. METHODS: Patients 16-65 years old attending hospital with minor head injury were invited to attend the clinic two weeks after presentation. A specialized brain injury nurse and/or assistant clinical psychologist assessed them. Patients with persistent symptoms were invited to a second assessment four weeks later. RESULTS: One thousand two hundred and fifty-five patients were invited for first assessment, the most common cause of head injury was assault (454) followed by road traffic accident (334). Six hundred and sixteen patients did not attend the first assessment; most of non-attendees were those who had been assaulted (281). Six hundred and thirty-nine patients attended, (472) were male, their mean age was 33. Forty-three per cent of them had history of recent alcohol intake. One third had had a previous head injury. Although 391 attendees were in regular employment, 219 patients were unable to return to work 2 weeks after discharge (56%), and 49 people were still off sick 6 weeks after the injury. The most common complaints at both assessments were fatigue, headache, dizziness, irritability, sleep disturbances, poor concentration and poor memory in that order. CONCLUSION: This study shows a significant number of patients with minor head injury still complaining of post concussive symptoms, which may contribute to a delay in return to work. The high incidence of non-attendance among the assaulted victims may indicate that this group needs to be more effectively targeted. Further study to look at the longer-term consequences of minor head injury is required in view of these findings.

Adolescent↗

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.

OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

Acetylcholine↗