Biomedical subjects

P P Chen

Publications and source records attributed to P P Chen.

At least 19 recordsLinked to original sources

PubMed2006

Postoperative outcome in Chinese patients having primary total knee arthroplasty under general anaesthesia/intravenous patient-controlled analgesia compared to spinal-epidural anaesthesia/analgesia.

OBJECTIVE: To compare postoperative outcomes in patients having primary total knee arthroplasty receiving general or regional anaesthesia. DESIGN: Randomised prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Patients having primary total knee replacement were randomised to either general anaesthesia followed by postoperative intravenous patient-controlled analgesia with morphine, or combined spinal-epidural anaesthesia followed by postoperative epidural infusion of bupivacaine 0.1% with fentanyl 2 microg/mL. MAIN OUTCOME MEASURES: Visual analogue scale pain scores, perioperative blood loss, time to first meal and ambulation, and prevalence of postoperative complications. RESULTS: Sixty consecutive patients were enrolled in this study. Postoperative median pain scores were consistently lower at 1 (P<0.0001), 6 (P=0.08), 12 (P=0.003), 24 (P=0.14), and 48 hours (P=0.007) in those given regional anaesthesia. Although there was a trend towards fewer complications in the latter group, there were no statistically significant differences between the two groups with respect to the incidence of postoperative blood loss, haemodynamic instability, pruritus, nausea, vomiting, urinary retention, or other surgical/medical complications. Postoperatively, patients given regional anaesthesia also resumed meals earlier (P<0.0001), and showed a trend towards earlier ambulation and hospital discharge. CONCLUSION: Chinese patients undergoing total knee arthroplasty with regional anaesthesia/regionally delivered analgesia enjoyed better postoperative pain relief and resumed meals earlier than those receiving general anaesthesia/intravenous patient-controlled analgesia. The former also showed trends towards less adverse effects, postoperative complications, earlier ambulation, and earlier hospital discharge.

Analgesia, Epidural↗

PubMed2005

Human monoclonal IgG anticardiolipin antibodies induce nitric oxide synthase expression.

OBJECTIVE: Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function. METHODS: Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels. RESULTS: Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS. CONCLUSION: Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.

Animals↗

PubMed2005

Antiphospholipid antibodies are associated with enhanced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model.

OBJECTIVE: Oxidative stress contributes to atherosclerosis, and evidence of enhanced oxidative stress exists in antiphospholipid syndrome (APS). In a non-lupus murine model, we evaluated whether anticardiolipin (aCL) antibodies could affect the oxidant/antioxidant balance as an early biochemical step of APS. METHODS: Hybridomas producing human and murine aCL and anti-beta(2)-glycoprotein I (abeta2-GPI) monoclonal antibodies were injected into three groups of five female BALB/c severe combined immunodeficiency (SCID) mice. Corresponding hybridomas secreting non-antiphospholipid antibodies of the same isotype were employed as controls. Sera and organs were collected after 30 days. Paraoxonase (PON) activity, peroxynitrite, superoxide, nitric oxide (NO) and nitrotyrosine were measured in plasma. Expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) was assessed by western blot and immunohistochemistry. RESULTS: PON activity and NO (sum of nitrate and nitrite) levels were reduced in the human aCL IgG group (P<0.002 and P<0.04, respectively), whilst peroxynitrite and superoxide and expression of total antioxidant capacity of plasma were increased (P<0.01). PON and NO were decreased in the murine abeta2-GPI IgG and IgM aCL groups (P<0.03 and P<0.05, respectively). Nitrotyrosine was elevated in the human aCL IgG group (P<0.03). Western blotting showed reduced iNOS expression in the hearts of the IgG aCL group, confirmed by immunostaining. PON inversely correlated with IgG aCL titres (P<0.001), superoxide (P<0.008) and peroxynitrite levels (P<0.0009). Peroxynitrite and total IgG aCL were independent predictors of PON (P<0.0009 and P<0.02, respectively). Superoxide was the only independent predictor of NO (P<0.008) and of nitrotyrosine (P<0.002). CONCLUSION: aCL antibodies are associated with the decreased PON activity and reduced NO that may occur in the preclinical phase of APS.

Animals↗

PubMed2005

A prospective evaluation of health-related quality of life in Hong Kong Chinese patients with chronic non-cancer pain.

OBJECTIVE: To evaluate the health-related quality of life in Hong Kong Chinese patients with chronic non-cancer pain. DESIGN: Prospective cross-sectional survey. SETTING: Regional public hospitals, Hong Kong. PATIENTS: Patients attending out-patient pain management clinics between 1 July 2002 and 28 February 2003 were approached to complete a set of standardised questionnaires. MAIN OUTCOME MEASURES: Demographic profiles, treatment modality, litigation, compensation, social welfare status, Hospital Anxiety Depression Scale, and Medical Outcomes Survey short-form health survey (SF36). RESULTS: Data from 166 patients were analysed. The median numeric pain rating score was 6 (interquartile range, 2-10). Work-related injury occurred in 34.3% of patients, while another 34% were involved in pain-related litigation and 32% were receiving disability or unemployment benefit. Sixty-four percent of patients were managed by three or more disciplines, while 54.8% were also receiving complimentary alternative medical treatment, mainly traditional Chinese medicine (49.7%). The Hospital Anxiety Depression Score indicated clinical anxiety or depression in 71.1% of patients. All SF36 subscale scores were lower than the local population norm. Unemployed patients had higher depression scores (P = 0.005), while students or retirees had lower physical functioning scores (P = 0.004). Patients who were single had higher role emotion scores than those who were married or separated/widowed (P = 0.011). Logistic regression analysis showed that younger age (odds ratio = 0.95), being married (6.62), work-related injury (15.63) or higher general scores (1.03) were more likely to be associated with litigation. Social welfare benefit was associated with unemployment (3.39) and a lower level of physical functioning (0.98). CONCLUSION: There was a high prevalence of clinical anxiety, depression, and severe impairment in the health-related quality of life in Hong Kong Chinese patients with chronic non-cancer pain. Specific factors affected the health-related quality of life, likelihood of litigation, and social benefit.

Adult↗

PubMed2004

Data management using the personal digital assistant in an acute pain service.

Handheld personal digital assistants (PDA) are increasingly being used by physicians for a variety of information and data management purposes. We evaluated a PDA-based data management system for our acute pain service. A structured questionnaire survey was conducted to assess staff experience and attitude towards the paper system before the introduction of the PDA, and three months after introduction of the PDA system. We compared the time taken to conduct the acute pain round before and after the implementation of the PDA. The time saved in data management and the amount of paper saved were estimated. Data from 177 patients with a total of 635 acute pain follow-up visits were entered over a three-month period. User satisfaction, ease of access to drug reference and clinical guidelines were similar between the two systems. The respondents found that the PDA was easy to use but less so than the paper system (P = 0.007), in particular, when accessing a patient's cumulative data (P = 0.007). There was no missed follow-up or data entry with the use of PDA. The time taken to attend follow-up visits was similar for the two systems (Paper: 8.8 +/- 3.2 compared to PDA: 7.0 +/- 2.0 minutes, P = 0.151). The estimated annual amount of paper and time saved in data management was 650 sheets and 130 man-hours respectively. Our experience with the use of the PDA in APS was satisfactory. The PDA system can potentially reduce time and paper use and missed data entry and patient follow-up.

Acute Disease↗

PubMed2004

Out-patient chronic pain service in Hong Kong: prospective study.

OBJECTIVE: To examine the profile and referral pattern of patients attending an out-patient pain management service in Hong Kong. DESIGN: Prospective cross-sectional survey. SETTING: Regional public hospitals, Hong Kong. PATIENTS: All patients attending out-patient pain management clinics in the New Territories East public hospitals between 1 September and 31 December 2002. MAIN OUTCOME MEASURES: Demographic profiles, referring specialty, pain diagnosis, pain sites, duration and severity of pain, treatment modality, litigation, compensation, and social welfare status. Data were collected using a standardised questionnaire. RESULTS: Two hundred and forty-eight patients were interviewed. Most patients (70%) were middle-aged, with 21% over 60 years. Seventy-nine percent of patients were referred to the clinics either from orthopaedic surgeons (64.1%), general and other surgeons (14.9%), or general practitioners (3.6%). The median (range) duration of pain was 2.3 (0.08-26.7) years. The most common pain diagnoses were musculoskeletal back pain (46.4%) and neuropathic pain (27.8%). A total of 11.3% of the patients had two pain diagnoses, while 40.7% complained of pain in more than one location. Pain in the limbs was the most frequent complaint followed by the head, neck, and back. Approximately 38% of patients had tried four or more treatment modalities. Oral medication was the most common method (86.7%) of pain-relief treatment. More than half of the patients had also tried physiotherapy and traditional Chinese medicine. Approximately 37% of the patients were unemployed, while 31% were receiving social security subsidy. Eighty-six patients had pain associated with a work-related injury, and of these patients, 80% were involved in compensation claims. CONCLUSIONS: The profile of patients referred to the pain management clinics was complex. Patients were mainly referred from specialists. The economic implication in this group of patients is likely to be significant as many patients utilised multiple treatment modalities, were unemployed and on social welfare benefits, and were involved in compensation and litigation proceedings.

Chronic Disease↗

PubMed2003

The effect of intra-operative video on patient anxiety.

We conducted a randomised controlled study to evaluate whether watching video compact discs intra-operatively using a liquid crystal display (LCD) unit decreased anxiety. Forty-four patients undergoing elective surgery under regional anaesthesia were assigned to either the LCD or control group. Anxiety was measured using the Chinese version of the State-Trait Anxiety Inventory (STAI) and visual analogue score (VAS). The mean (SD) anxiety trait scores were 46.15 (6.28) and 46.40 (7.32) in the control and LCD groups, respectively. The state anxiety of the LCD group [35.50 (7.96)] measured immediately postoperatively was significantly lower than the control group [41.50 (9.02); p = 0.03]. The median (range) reduction in VAS anxiety score was not significantly greater in the LCD group [20 (20 to 80) mm] compared with the control group [12.5 (70 to 60) mm]. Watching video intra-operatively reduces patient anxiety as measured by the STAI.

Adolescent↗

PubMed2003

The effect of an alveolar recruitment strategy on oxygenation during laparascopic cholecystectomy.

This prospective randomized controlled trial examined the effect of an "alveolar recruitment strategy" (ARS) in healthy patients having laparoscopic cholecystectomy. Twenty-four consecutive ASA 1 or 2 patients were randomly allocated to an ARS or control group. All patients were manually ventilated to a maximal airway pressure of 25 to 30 cmH2O or a tidal volume of 10 ml/kg during induction of general anaesthesia. After intubation, the control group was ventilated with standardized mechanical ventilation settings. The ARS group was manually ventilated to an airway pressure of 40 cmH2O for 10 breaths over one minute, followed by mechanical ventilation with similar standardized settings plus 5 cmH2O positive end-expiratory pressure. Blood pressure, heart rate, arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) was measured pre-induction, 20 minutes post induction but before abdominal insufflation, 20 minutes after abdominal insufflation, and 20 minutes after arrival in the recovery room. Demographic and operation data were similar. The ARS group pre-insufflation PaO2 [30.16 (9.43)] was higher than the control group [22.19 (9.08)] (P = 0.047). There was a significant difference in PaO2 between the ARS [23.94 (4.87)] and control [17.26 (3.93)] groups during the post-insufflation period (P = 0.001). There were no significant differences in PaO2 between the groups during baseline and recovery periods. No adverse effects were reported. ARS improved arterial oxygenation intraoperatively in healthy patients having laparoscopic cholecystectomy, without clinical cardiovascular compromise or respiratory complication. We conclude that this alveolar recruitment strategy is a useful method of increasing arterial oxygenation.

Adolescent↗

PubMed2003

Hong Kong Chinese teachers' attitudes towards life-sustaining treatment in the dying patients.

OBJECTIVE: To evaluate the attitudes of Hong Kong Chinese teachers towards life-sustaining treatment in the dying patients. DESIGN: Prospective structured questionnaire survey. SETTING: Hong Kong Institute of Education. SUBJECTS AND METHODS: All teaching staff at the Hong Kong Institute of Education were sent the survey questionnaire. The questionnaire gathered demographic data, information on experience of 'life and death' decision-making, and views on life-sustaining treatment decisions. Respondents were also requested to respond to statements on life-sustaining treatment using a 5-point Likert Scale (1 representing strong disagreement and 5 representing strong agreement). RESULTS: A total of 436 questionnaires were sent to teaching staff at the Hong Kong Institute of Education. The response rate was 27.8%. More than half (65.8%) of the respondents were aged between 30 and 49 years. There was an equal proportion of men and women among respondents. The respondents agreed with statements supporting end-of-life decisions (mean aggregate score, 3.13; standard deviation, 1.24; P<0.0001), and disagreed with statements against such decisions (mean aggregate score, 2.81; standard deviation, 1.22; P<0.0001). If the patient is competent, half of the respondents agreed that the patient alone should make the decision, while 27.2% believed that it should be a joint decision made by the patient, the family, and the doctor. Conversely, if the patient is incompetent, 52.6% agreed that it should be a joint decision made by the family and the doctor. There was strong support for advanced directives, whereby decisions in relation to life-sustaining treatment were legally recorded in advance (mean score, 3.62; P=0.0001). CONCLUSION: The teachers in this survey appear to support the practice of withdrawing and withholding life-sustaining treatment in the dying patients when medical treatment is considered futile. Although patient autonomy in decision-making was supported by the greatest number of respondents, joint decision-making by the patient, family members, and doctors was also favoured by a substantial group. There was strong support for the use of advanced directives with respect to life-sustaining treatment.

Adult↗

PubMed2003

Status of obstetric epidural analgesia services in Hong Kong public hospitals: postal questionnaire survey.

OBJECTIVE: To examine the status of obstetric epidural analgesia services in Hong Kong public hospitals in 2001, and to compare findings with those from a similar survey conducted in 1995. DESIGN: Postal questionnaire survey. SETTING: Hospital Authority hospitals in Hong Kong offering an obstetric and delivery service. PARTICIPANTS: Chiefs of Service of departments of anaesthesia and coordinators of obstetric anaesthesia and analgesia service. MAIN OUTCOME MEASURES: The availability of an obstetric epidural analgesia service, specialist staff allocation to the service, existence of clinical protocols, rate of epidural analgesia, techniques of epidural administration, obstetric outcome or mode of delivery, and the incidence of adverse events associated with the use of epidural analgesia. RESULTS: Between 1 January and 31 December 2001, all eight Hospital Authority hospitals with an obstetric service provided epidural analgesia for labour pain relief, but only six (75%) offered a 24-hour service. A dedicated anaesthetist provided obstetric anaesthesia and analgesia during office hours in all units, but after hours in only three. This level of service provision compared favourably with that available in 1995, when only 82% of public maternity units provided epidural analgesia and only 36% offered a 24-hour service. The median epidural analgesia rate was 15% (range, 8%-20%) compared with 10% in 1995. The incidence of adverse events and complications was very low. Formal written protocols for the conduct of epidural analgesia for labour were used in six units. All units used mixtures of local anaesthetic combined with opioid, administered as intermittent boluses, continuous epidural infusion, or patient-controlled epidural analgesia. CONCLUSIONS: Although there has been progress and improvement in the provision of obstetric epidural analgesia services in our public hospitals, the rate is still relatively low and the provision of services after hours is limited. Further progress will likely be hindered by current or future cutbacks in public hospital budgets.

Analgesia, Epidural↗

PubMed2002

Patient-controlled epidural analgesia in a parturient with hypertrophic obstructive cardiomyopathy.

We describe the use of patient-controlled epidural analgesia (PCEA) using fentanyl in the management of a labouring parturient with hypertrophic obstructive cardiomyopathy (HOCM). With non-invasive monitoring, PCEA was started in the early first stage of labour with a bolus dose of fentanyl 20 microg, lockout 5 min and 4-h maximum dose of 500 microg. Analgesia was satisfactory during the early first stage but was poor subsequently, despite a total fentanyl consumption of 760 microg during the 6-h labour. The maternal cardiovascular condition was stable throughout labour and delivery and the baby was born in good condition without subsequent respiratory depression. Opioid-based PCEA is an alternative to systemic analgesia in labouring parturients with HOCM. However, although its use avoids the potential adverse effects of sympathetic block associated with conventional epidural analgesia, our regimen had limited analgesic efficacy in the latter stage of labour.

Journal Article↗

PubMed2002

Tracheobronchial injury secondary to blunt chest trauma: diagnosis and management.

Tracheobronchial injury is an uncommon complication in blunt chest trauma. The typical clinical features include haemoptysis, dyspneoa, and air leak. Tracheobronchial injury occurs after high energy impact and is commonly associated with injuries of other vital organs. If tracheobronchial injury is undetected and left untreated, it may cause persistent air leak which can render ventilation difficult and inefficient. Diagnosis of tracheobronchial injury should be made and confirmed by flexible bronchoscopy. The essence of airway management is to bypass the lesion by means of endobronchial intubation to the healthy bronchus with a single-lumen or double-lumen endotracheal tube. Such manoeuvres can also facilitate surgical access if thoracotomy is indicated. Taking into account the size of the lesion and the resulting respiratory status, surgical reconstruction of the injured airway is often necessary. More severe injury may even require lobectomy or pneumonectomy. Late complications of untreated tracheobronchial injury include bronchial stenosis, recurrent pneumonia and bronchiectasis. Prompt diagnosis and treatment generally lead to good functional recovery.

Bronchi↗

PubMed2002

The application of clinical simulation in crisis management training.

Since it was first introduced more than 30 years ago, clinical simulation has become a popular tool for medical training, particularly in crisis management. The modern high-fidelity patient simulator consists of a whole-body mannequin with integrated electronic patient monitoring; it is controlled by computers capable of simulating numerous clinical scenarios and patient characteristics, and reacting to various interventions appropriately. Simulator training is theoretically superior to conventional training in management of rare crisis situations, as it allows unlimited practice in a safe yet familiar environment. Training in clinical skills can be developed, together with competency in crisis management behaviours such as leadership and communication skills. Although there is evidence demonstrating the popularity, reliability, and validity of simulator training, its superiority over conventional training has not been proven, and research in this area is required.

Anesthesiology↗

PubMed2002

Recall of preoperative anaesthesia information in Hong Kong Chinese patients.

OBJECTIVE: To evaluate the ability of patients to recall information provided during a preoperative visit. DESIGN: Qualitative study. SETTING: Regional hospital, Hong Kong. PATIENTS: Sixty patients scheduled for elective surgery under general anaesthesia or central neuro-axial block. MAIN OUTCOME MEASURES: Satisfactory recall of preoperative information, defined as the ability to remember at least 75% of adverse effects described. RESULTS: Fifty-nine (98.3%) patients were satisfied with the preoperative information. Forty-two (70%) patients rated anaesthetic complications as important. At the interview on the day of the operation, 57 (95%) patients had satisfactory recall of the information provided. Eighty-five percent of patients remembered that the information was provided by an anaesthesiologist. After the operation, of those who experienced adverse effects, 48 (96%) patients remembered being told to anticipate the adverse anaesthetic event. Univariate analysis found that age, sex, education level, occupation, and the modality of anaesthesia did not affect patient recall of preoperative information on the day of surgery or 1 day postsurgery. CONCLUSION. There was satisfactory recall of preoperative information by the majority of patients in the study. Most patients expressed satisfaction with the information provided.

Adult↗

PubMed2002

Acute pain services in Hong Kong: facilities, volume, and quality.

Acute pain services in public hospitals in Hong Kong were studied. Audit data on the volume and quality of acute pain services were collected prospectively from 1997 to 1999, and data on related facilities were collected in 2000. About 20% of patients undergoing a major operation received an acute pain service; of these, 78.6% were satisfied with the treatment provided. In 2000, 86% (18/21) of hospitals providing anaesthetic services were running an acute pain service. Staffing was better in hospitals providing a high volume of acute pain services, ranging from a full-time specialist anaesthesiologist assisted by a half-time trainee to a half-time specialist assisted by a full- or half-time trainee. However, only four hospitals were staffed with pain nurses. In total, 57% of patients received intravenous patient-controlled analgesia and 32% epidural analgesia. The mean duration of acute pain service treatment was 3.1 days. Currently anaesthesiologist-based acute pain services take care of a limited number of patients. To expand the coverage, there should be a move towards an anaesthesiologist-led, pain nurse-based, acute pain service. The present shortage of pain nurses should be addressed.

Analgesia, Patient-Controlled↗

PubMed2001

Identification of anti-thrombin antibodies in the antiphospholipid syndrome that interfere with the inactivation of thrombin by antithrombin.

The combined presence of anti-phospholipid (PL) Ab, including lupus anticoagulants (LAC) and/or anticardiolipin Ab (aCL), and thrombosis is recognized as the antiphospholipid syndrome (APS). LAC are detected as an inhibitory effect on PL-restricted in vitro blood coagulation tests, and are comprised mainly of Ab against beta(2) glycoprotein I and prothrombin (PT). Recently, anti-PT Ab (aPT) were found to be associated with thrombosis by some investigators, although this is not confirmed by others. Considering that aPT are heterogeneous in patients and that PT is converted into thrombin, we hypothesize that certain aPT in patients may bind to thrombin, and that some of such anti-thrombin Ab may interfere with thrombin-antithrombin (AT) interaction and thus reduce the AT inactivation of thrombin. To test this hypothesis, we searched for anti-thrombin Ab in APS patients and then studied those found for their effects on the AT inactivation of thrombin. The results revealed that most, but not all, aPT-positive patient plasma samples contained anti-thrombin Ab. To study the functional significance of these Ab, we identified six patient-derived mAb that bound to both PT and thrombin. Of these mAb, three could reduce the AT inactivation of thrombin, whereas others had minimal effect. These findings indicate that some aPT in patients react with thrombin, and that some of such anti-thrombin Ab could inhibit feedback regulation of thrombin. Because the latter anti-thrombin Ab are likely to promote clotting, it will be important to develop specific assays for such Ab and study their roles in thrombosis in APS patients.

Adolescent↗

PubMed2001

Detection of elevated serum beta-chemokine levels in seronegative Chinese individuals exposed to human immunodeficiency virus type 1.

The mutations in the CCR5 coding region, such as CCR5Delta32 and CCR5m303, that suppress the transmission of human immunodeficiency virus (HIV) type 1 do not exist in Chinese people. However, 9 Chinese subjects in Taiwan with histories of multiple sexual exposures to HIV remained uninfected, suggesting that certain anti-HIV factors do indeed exist. Experiments were therefore designed to investigate the immune mechanism that protects this cohort against HIV infection. Peripheral blood samples from these 9 subjects and 7 healthy people who had not been exposed to HIV were obtained for the quantitation of the levels for beta-chemokines and interleukin 16 (IL-16) in serum samples or secreted by peripheral blood lymphocytes. Significantly higher serum levels for nearly all 3 beta-chemokines, regulation on activation, normal T cell-expressed and secreted, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta (P<.05, P<.05, and P=.05, respectively), but not IL-16, were detected in the 9 HIV-uninfected subjects as compared with control subjects. The result suggests that among the host genes and cellular factors thus far identified, beta-chemokines are the major HIV-suppressive factors that protect Chinese people from infection with HIV.

Adult↗

PubMed2001

Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein.

BACKGROUND: We recently suggested that many anticardiolipin antibodies bind only to oxidized cardiolipin (OxCL) and/or to OxCL-beta(2)-glycoprotein 1 (beta(2)GP1) adducts but not to a "reduced" cardiolipin that is unable to undergo oxidation. To test this hypothesis, we investigated 24 sera, 4 protein A-purified IgG fractions, and 3 human monoclonal antibodies that were all isolated from patients with antiphospholipid antibody syndrome (APS); testing was also performed in 7 controls. Two monoclonal antibodies (IS3 and IS4) were selected for binding to CL and one was selected for binding to beta(2)GP1 (LJB8). METHODS AND RESULTS: By chemiluminescent immunoassay, all APS sera samples bound only to OxCL and not to reduced CL, and the binding was inhibited >95% by OxCL but not reduced CL. All purified IgG fractions bound to beta(2)GP1 but only when the beta(2)GP1 was plated on microtiter wells coated with OxCL. All 3 monoclonal antibodies bound only to OxCL. On Western blots, IS4 and LJB8 bound to beta(2)GP1 as well as to delipidated apoB of oxidized LDL but not to native apoB. IS3 also bound to oxidized apoB on Western blot. Covalent modification of beta(2)GP1 with oxidation products of CL made it more antigenic for APS serum samples, for purified IgG fractions, and for the monoclonal antibodies. CONCLUSIONS: These data support the hypothesis that oxidation of CL is needed to generate epitopes for many anticardiolipin antibodies and that some of these epitopes are covalent adducts of OxCL with beta(2)GP1 or apoB.

Antibodies, Anticardiolipin↗