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L S Chan

Publications and source records attributed to L S Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pemphigoid nodularis associated with autoantibodies to the NC16A domain of BP180 and a hyperproliferative integrin profile.

Pemphigoid nodularis, a rare variant of bullous pemphigoid, has clinical features resembling prurigo nodularis, with blisters arising from normal-appearing or nodular skin. The fine antigenic epitope of the autoantibodies and the mechanism accounting for the nodular phenotype has not been delineated. We describe a patient with pemphigoid nodularis that fulfilled the criteria of bullous pemphigoid by histopathologic examination and direct and indirect immunofluorescence studies. Immunopathologic examination also revealed in situ deposition and circulating autoantibodies of all IgG subclasses, except IgG3, and both light chains to the patient's skin basement membrane. By immunoblotting, the patient's IgG autoantibodies labeled BP180, BP230, and an unidentified 150-kd epidermal protein and mapped the BP180 epitope to the MCW-1, region 2 of the NC16A domain. The nodular plaque skin showed expression of alpha-6 and beta-1 integrin subunits, mediators of matrix-cell signaling and proliferation, at the basal and the suprabasal epidermis, a pattern found in psoriasis, which is the prototype of hyperproliferative dermatoses.

Aged↗
PubMed2001

Selective nonoperative management in 1,856 patients with abdominal gunshot wounds: should routine laparotomy still be the standard of care?

OBJECTIVE: To evaluate the safety of a policy of selective nonoperative management (SNOM) in patients with abdominal gunshot wounds. SUMMARY BACKGROUND DATA: Selective nonoperative management is practiced extensively in stab wounds and blunt abdominal trauma, but routine laparotomy is still the standard of care in abdominal gunshot wounds. METHODS: The authors reviewed the medical records of 1,856 patients with abdominal gunshot wounds (1,405 anterior, 451 posterior) admitted during an 8-year period in a busy academic level 1 trauma center and managed by SNOM. According to this policy, patients who did not have peritonitis, were hemodynamically stable, and had a reliable clinical examination were observed. RESULTS: Initially, 792 (42%) patients (34% of patients with anterior and 68% with posterior abdominal gunshot wounds) were selected for nonoperative management. During observation 80 (4%) patients developed symptoms and required a delayed laparotomy, which revealed organ injuries requiring repair in 57. Five (0.3%) patients suffered complications potentially related to the delay in laparotomy, which were managed successfully. Seven hundred twelve (38%) patients were successfully managed without an operation. The rate of unnecessary laparotomy was 14% among operated patients (or 9% among all patients). If patients were managed by routine laparotomy, the unnecessary laparotomy rate would have been 47% (39% for anterior and 74% for posterior abdominal gunshot wounds). Compared with patients with unnecessary laparotomy, patients managed without surgery had significantly shorter hospital stays and lower hospital charges. By maintaining a policy of SNOM instead of routine laparotomy, a total of 3,560 hospital days and $9,555,752 in hospital charges were saved over the period of the study. CONCLUSION: Selective nonoperative management is a safe method for managing patients with abdominal gunshot wounds in a level 1 trauma center with an in-house trauma team. It reduces significantly the rate of unnecessary laparotomy and hospital charges.

Abdominal Injuries↗
PubMed2001

Evidence assessment of management of acute otitis media: I. The role of antibiotics in treatment of uncomplicated acute otitis media.

CONTEXT: In 1995, >5 million episodes of acute otitis media (AOM) accounted for $3 billion in health care expenditures. OBJECTIVES: To synthesize the literature on the natural history of AOM, the effectiveness of antibiotic treatment in uncomplicated AOM, and the relative effectiveness of specific antibiotic regimens. DATA SOURCES: Seven electronic databases for articles published between 1966 and March 1999 and reference lists in proceedings, published articles, reports, and guidelines. STUDY SELECTION: Two physicians independently assessed each article. Studies addressing AOM in children 4 weeks to 18 years old were included; those addressing children with immunodeficiencies or craniofacial abnormalities were excluded. Randomized, controlled trials (RCTs) were used to assess antibiotic effectiveness, and RCTs and cohort studies were used to assess the natural history of AOM. Among the 3491 citations identified, 80 (2.3%) met our inclusion criteria. DATA EXTRACTION: Two physicians independently abstracted data and assessed the quality of studies using a validated scale for RCTs and 8 quality components for cohort studies. DATA SYNTHESIS: Random-effects estimates of pooled absolute rate differences of outcomes were derived, and heterogeneity of both the rates and rate differences was assessed. Children with AOM not treated with antibiotics experienced a 1- to 7-day clinical failure rate of 19% (95% confidence interval: 0.10-0.28) and few suppurative complications. When patients were treated with amoxicillin, the 2- to 7-day clinical failure rate was reduced to 7%, a 12% (95% confidence interval: 0.04-0.20) reduction. Adverse effects, primarily gastrointestinal, were more common among children on cefixime than among those on ampicillin or amoxicillin. They were also more common among children on amoxicillin-clavulanate than among those on azithromycin. CONCLUSIONS: The majority of uncomplicated cases of AOM resolve spontaneously without apparent suppurative complications. Ampicillin or amoxicillin confers a limited therapeutic benefit. There is no evidence to support any particular antibiotic regimens as more effective at relieving symptoms. Certain antibiotics are more likely than others to cause diarrhea and other adverse events.

Acute Disease↗
PubMed2001

Evidence assessment of management of acute otitis media: II. Research gaps and priorities for future research.

OBJECTIVES: To report research gaps and priorities of future research identified during an evidence assessment process on the management of acute otitis media (AOM). METHODS: A conceptual framework for management of AOM was developed to guide the evidence assessment. An 11-member technical expert panel guided the selection of key questions, prioritization of influencing factors, development of scope, definition of AOM, and search strategy through polling processes and conference calls. Quality of clinical trials was evaluated using established scales. Outcome measures were abstracted from each study. RESULTS: A total of 3461 titles and abstracts were screened, and 760 full-length articles were reviewed. Of the 760 articles, 80 studies addressed the key questions. In defining AOM, 42 (52.5%) of the 80 studies included the middle-ear effusion component, only 2 (2.5%) included the rapid onset component, and 26 (32.5%) included the signs/symptoms of inflammation component. None of the 80 studies used all 3 components. Of the 74 controlled trials, 39 (53%) were of acceptable quality (Jadad score of 3 or higher). The technical experts did not agree in the ranking of the importance of the 41 influencing factors (Kendall's coefficient of concordance was 0.0022). Another poll also indicated diverse opinions of the experts on the importance of 7 key questions derived from the conceptual framework (Kendall coefficient of concordance is 0.21). Furthermore, our review found that the type and definition of outcome measure varied. CONCLUSIONS: Despite the large body of literature on AOM, its quality is uneven and its findings are not generalizable. Future research should try to answer all key questions and investigate all risk factors in well-designed, scientific studies.

Acute Disease↗
PubMed2000

Equine bullous pemphigoid IgG autoantibodies target linear epitopes in the NC16A ectodomain of collagen XVII (BP180, BPAG2).

Bullous pemphigoid (BP) is an autoimmune subepithelial blistering dermatosis of humans, dogs, cats and pigs. It is characterized by skin-fixed and circulating IgG autoantibodies that target one or both BP antigens. An immunological homologue of BP in humans was diagnosed in two horses with cutaneous and mucosal ulcerations as well as microscopic subepithelial vesiculation. Immunological investigations revealed similar findings for both the horses. Direct immunofluorescence demonstrated the presence of IgG deposited linearly at the dermoepidermal junction in mucosal and skin biopsy specimens. Indirect immunofluorescence testing confirmed the existence of circulating basement membrane-specific IgG autoantibodies. Using intact and salt-split epithelial substrates, serum IgG were shown to target antigens situated not only at the basal, but also at the lateral and apical aspects of stratum basale keratinocytes. Immunoblotting and ELISA corroborated that the IgG from affected horses, but not those from normal controls, exhibited high immunoreactivity against the NC16A extracellular domain of type XVII collagen (BPAG2, BP180). Equine BP could be proposed, therefore, as another spontaneous model of this most common basement membrane autoimmune dermatosis of humans.

Animals↗
PubMed2000

Molecular cloning of canine bullous pemphigoid antigen 2 cDNA and immunomapping of NC16A domain by canine bullous pemphigoid autoantibodies.

The autoantibody-mediated subepidermal blistering skin disease bullous pemphigoid affects both humans and dogs. We previously demonstrated that canine bullous pemphigoid patient's autoantibodies targeted skin basement membrane component and a 180-kDa keratinocyte protein. We extend our works to partially isolate the cDNA encoding canine bullous pemphigoid antigen 2 (BPAg2, BP180). Total RNA extracted from a papillomavirus-immortalized canine keratinocyte cell line and a cultured canine squamous carcinoma cell line SCC 2/88 were used to isolate fragments of cDNA encoding BPAg2 by reverse transcription-PCR and 5'-rapid amplification of cDNA end. The isolated sequence included the 5'-untranslated region, the entire intracellular, transmembranous, and extracellular NC16A autoantigenic domains, plus a small segment of the collagenous domain. Sequence analyses of the isolated cDNA showed 87 and 85% identities between canine and human at the nucleotide sequence and at the deduced amino acid sequence levels, respectively. The canine BPAg2 sequence was confirmed by a rabbit antibody raised against a 18-amino acid peptide deduced from the canine NC16A nucleotide sequence. Autoantibodies from canine bullous pemphigoid patients' sera recognized epitopes within the human NC16A domain. The cloning of the cDNA encoding this disease-associated protein may allow us to develop a canine model in dissecting the immunopathologic mechanism underlying bullous pemphigoid.

Animals↗
PubMed2000

Nonoperative management of splenic injuries: have we gone too far?

HYPOTHESIS: Patients with severe blunt injuries to the spleen have a high likelihood of failing nonoperative management of splenic injuries (NOMSI). DESIGN: Review of medical records, helical computed tomographic imaging data, and trauma registry data. SETTING: Academic level I trauma center at a large county hospital. PATIENTS: A total of 105 patients with blunt trauma to the spleen, admitted between January 1995 and December 1998, who survived more than 48 hours and had complete records. Of these patients, 53 (56%) were selected for NOMSI. The splenic injury was graded by the Organ Injury Scale of the American Association for the Surgery of Trauma (grades I to V, with grade V being the worst possible injury). MAIN OUTCOME MEASURES: Failure of NOMSI, defined as the need for operation to the spleen after a period of nonoperative management. RESULTS: Compared with patients who had successful NOMSI, the 29 patients (52%) in whom NOMSI failed were older and more severely injured. They also required extra-abdominal operations more frequently, underwent transfusion with more units of blood while being managed nonoperatively, and had higher grades of splenic injury. Splenic injury grade III or higher and transfusion of more than 1 U of blood were identified as independent risk factors for failure of NOMSI. The existence of both risk factors predicted failure in 97% of cases. The grading by computed tomography correlated well with the actual injury to the spleen as seen at operation. CONCLUSIONS: In patients with high-grade splenic injuries who require a transfusion of more than 1 U of blood, NOMSI is very likely to fail. Decreasing the threshold for operation or intensifying the monitoring is highly recommended for such patients.

Adult↗
PubMed2000

A spontaneously arising porcine model of bullous pemphigoid.

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease targeting the hemidesmosomal proteins bullous pemphigoid antigens 1 and 2. Currently, there is no active animal model in which to dissect the immunopathogenic mechanism. We noticed that cutaneous blistering arose spontaneously in 12 adult Yucatan minipigs. Skin lesions consisted of turgid, isolated or clustered vesicles that occasionally evolved from erythematous and pruritic patches. Histopathological examination revealed subepidermal vesicles rich in intact and degranulated eosinophils. Antigen mapping and transmission electron microscopy confirmed that dermoepidermal separation took place in the lamina lucida of the epidermal basement membrane zone. Direct immunofluorescence revealed the presence of IgG deposited linearly at the dermoepidermal junction in seven of nine skin specimens examined. Indirect immunofluorescence testing confirmed the presence, in the serum from eight of eight affected pigs, of circulating basement membrane-specific IgG autoantibodies (titers 1 : 50 to 1 : 250). Using uncleaved and salt-split lip substrates, the autoantibodies were shown to target antigens situated not only at the basal, but also at the lateral and apical aspects of stratum basale keratinocytes. Immunoelectron microscopy confirmed that circulating IgG autoantibodies recognized hemidesmosomal antigen(s). ELISA, immunoblotting and immunoadsorption demonstrated that five of eight serum samples exhibited high immunoreactivity against BPAG2-NC16A peptides. This novel porcine acquired blistering dermatosis could be proposed as a valuable model to conduct immunomechanistic studies on the natural progression of BP, correlation of autoreactive T cells or autoantibodies with disease activity, and the role of eosinophils in the blistering process, as these diseases cannot be modeled easily in human patients or in murine passive transfer models.

Amino Acid Sequence↗
PubMed2000

Autoimmune blistering skin diseases.

Emergency physicians, at the front line of patient care, are often confronted with a wide variety of dermatologic conditions. Prompt recognition is essential, especially for the autoimmune blistering skin diseases, many of which have considerable morbidity and mortality. Therefore, an accurate diagnosis is imperative for appropriate referral and initiation of therapy. This review article provides a concise yet thorough discussion of the clinical presentation, incidence, differential diagnosis and management of the commonly encountered autoimmune blistering skin diseases, some of which include pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita.

Adult↗
PubMed2000

Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype.

Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are blistering skin diseases characterized by IgG autoantibodies that predominantly target the noncollagenous domain 1 of type VII collagen, a skin basement membrane component. The basic immunologic events leading to the blistering processes in these diseases remains unclear. We defined the subclass and light chain compositions of the IgG autoantibodies in 15 patients, in order to gain insight into the blistering mechanism. Immunofluorescence correlated the patients' in vivo-bound and circulating antibasement membrane autoantibodies. Four eukaryotic recombinant proteins, including one full-length and three truncated noncollagenous domain 1 proteins generated by sequential deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoantibodies. The majority of patients' autoantibodies contained both complement-activating and non-complement-activating IgG subclasses. The presence or absence of complement-activating IgG autoantibody subclasses did not correlate with the inflammatory or noninflammatory clinical phenotype. The majority of tested sera contained both kappa and lambda light chain autoantibodies. All sera that reacted to the full-length noncollagenous domain 1 also reacted to the smallest truncated protein containing the cartilage matrix protein and the first three fibronectinlike repeats. The patients' anti-type VII collagen autoantibodies, likely to be polyclonal in nature, may contribute to the pathogenesis of the blistering process by both complement-dependent inflammatory injury and complement-independent mechanical disruption of the anchoring function of type VII collagen. The N-terminal region of the noncollagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies.

Autoantibodies↗
PubMed2000

Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant.

A subset of pemphigus herpetiformis, a rare pemphigus variant, is characterized histopathologically by subcorneal acantholysis and neutrophilic infiltration. The mechanism of neutrophil infiltration is unknown, but chemokines such as IL-8 may play a role. We investigated the possible role of IL-8 in two such cases. Direct and indirect immunofluorescence studies demonstrated in vivo-bound and circulating IgG epithelial cell surface-binding autoantibodies, both predominated by IgG4 subclass. ELISA and immunoblotting studies revealed that the patients' IgG autoantibodies recognized recombinant desmoglein 1 but not desmoglein 3. Preadsorption of the patients' sera with recombinant desmoglein 1 completely removed the epidermal cell surface immunostaining. Significantly, immunohistochemistry demonstrated intense expression of IL-8, co-localized with in vivo-bound IgG, in the upper epidermis, where the acantholysis took place. Affinity-purified sera IgG from these two patients, a normal individual, and a pemphigus vulgaris patient containing desmoglein 1 autoantibodies, were incubated with normal human keratinocytes in vitro. Cells treated with these patients' IgG secreted a seven-to-nine-fold increase of IL-8 (30-37 pg/ml) compared with the controls (2-4 pg/ml) and expressed a higher intensity of cytoplasmic IL-8 staining. These data demonstrate a novel functional role for IL-8 in the pathogenesis of the neutrophil-dominant subset of pemphigus herpetiformis. The autoantibody-induced epidermal cell IL-8 expression may represent a novel mechanism of epidermal neutrophil recruitment.

Adult↗
PubMed2000

Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial.

OBJECTIVE: To evaluate the effect of early optimization in the survival of severely injured patients. SUMMARY BACKGROUND DATA: It is unclear whether supranormal ("optimal") hemodynamic values should serve as endpoints of resuscitation or simply as markers of the physiologic reserve of critically injured patients. The failure of optimization to produce improved survival in some randomized controlled trials may be associated with delays in starting the attempt to reach optimal goals. There are limited controlled data on trauma patients. METHODS: Seventy-five consecutive severely injured patients with shock resulting from bleeding and without major intracranial or spinal cord trauma were randomized to resuscitation, starting immediately after admission, to either normal values of systolic blood pressure, urine output, base deficit, hemoglobin, and cardiac index (control group, 35 patients) or optimal values (cardiac index >4.5 L/min/m2, ratio of transcutaneous oxygen tension to fractional inspired oxygen >200, oxygen delivery index >600 mL/min/m2, and oxygen consumption index >170 mL/min/m2; optimal group, 40 patients). Initial cardiac output monitoring was done noninvasively by bioimpedance and, subsequently, invasively by thermodilution. Crystalloids, colloids, blood, inotropes, and vasopressors were used by predetermined algorithms. RESULTS: Optimal values were reached intentionally by 70% of the optimal patients and spontaneously by 40% of the control patients. There was no difference in rates of death (15% optimal vs. 11% control), organ failure, sepsis, or the length of intensive care unit or hospital stay between the two groups. Patients from both groups who achieved optimal values had better outcomes than patients who did not. The death rate was 0% among patients who achieved optimal values compared with 30% among patients who did not. Age younger than 40 years was the only independent predictive factor of the ability to reach optimal values. CONCLUSIONS: Severely injured patients who can achieve optimal hemodynamic values are more likely to survive than those who cannot, regardless of the resuscitation technique. In this study, attempts at early optimization did not improve the outcome of the examined subgroup of severely injured patients.

Adult↗
PubMed2000

Prevention of venous thromboembolism after injury: an evidence-based report--part I: analysis of risk factors and evaluation of the role of vena caval filters.

BACKGROUND: Trauma surgeons use a variety of methods to prevent venous thromboembolism (VT). The rationale for their use frequently is based on conclusions from research on nontrauma populations. Existing recommendations are based on expert opinion and consensus statements rather than systematic analysis of the existing literature and synthesis of available data. The objective is to produce an evidence-based report on the methods of prevention of VT after injury. METHODS: A panel of 17 national authorities from the academic, private, and managed care sectors helped design and review the project. We searched three electronic databases (MEDLINE, EM-BASE, and Cochrane Controlled Trial Register) to identify articles relevant to four key questions: methods of prophylaxis, methods of screening, risk factors for VT, and the role of vena caval filters. The initial 4,093 titles yielded 73 articles for meta-analysis. A random-effects model was used for all pooled results. Study quality was evaluated by previously published quality scores. In this article (part I), we report on the question ranked by the experts as the most important, i.e., Which is the best method to prevent VT?, and also on the incidence of deep venous thrombosis and pulmonary embolism in trauma patients. RESULTS: The incidence of deep venous thrombosis and pulmonary embolism reported in different studies varies widely. The pooled rates are 11.8% for deep venous thrombosis and 1.5% for pulmonary embolism. Only a few randomized controlled trials have evaluated the methods of VT prophylaxis among trauma patients, and combining their data is difficult because of different designs and preventive methods used. The quality of most studies is low. Meta-analysis shows no evidence that low-dose heparin, mechanical prophylaxis, or low-molecular-weight heparin are more effective than no prophylaxis or each other. However, the 95% confidence intervals of many of the comparisons are wide; therefore, a clinically important difference may exist. CONCLUSION: The trauma literature on VT prophylaxis provides inconsistent data. There is no evidence that any existing method of VT prophylaxis is clearly superior to the other methods or even to no prophylaxis. Our results cast serious doubt on the existing policies on VT prophylaxis, and we call for a large, high-quality, multicenter trial that can provide definitive answers.

Evidence-Based Medicine↗
PubMed2000

Prevention of venous thromboembolism after injury: an evidence-based report--part II: analysis of risk factors and evaluation of the role of vena caval filters.

OBJECTIVE: In part II, we describe the results of the literature search and data analysis concerning risk factors for venous thromboembolism and the role of vena caval filters (VCF) in preventing pulmonary embolism. METHODS: The methodology used in part I was used in part II. RESULTS: Spinal fractures and spinal-cord injuries increase the risk for development of deep venous thrombosis (DVT) by twofold and threefold, respectively. Patients with DVT were an average of 9 years older than patients without DVT. No specific age cut-off point for increased risk could be established because data could not be combined across studies. Patients with prophylactically inserted VCF had a lower incidence of pulmonary embolism (0.2%) compared with concurrently managed patients without VCF (1.5%) or historical controls without VCF (5.8%). These results are reported on uncontrolled studies with observational design. CONCLUSION: Spinal injuries, spinal cord injuries, and age are risk factors for development of DVT. Prophylactic placement of VCF in selected trauma patients may decrease the incidence of pulmonary embolism. Future research with well-designed studies is required to provide definitive answers.

Evidence-Based Medicine↗
PubMed2000

Fetal death after trauma in pregnancy.

Trauma in pregnancy places the mother and fetus at risk. The objective of this study is to identify risk factors independently associated with acute termination of pregnancy and/or fetal mortality after trauma. The medical and trauma registry records of 80 injured pregnant patients were reviewed. Data were collected and then analyzed by univariate and multivariate analysis. Three patients died (3.7%), 23 had the pregnancy acutely terminated (30%), and 14 suffered fetal death (17.5%). The only independent risk factors for fetal mortality were an Injury Severity Score (ISS) > or =9 and a nonviable pregnancy (<23 weeks). The combination of both risk factors increased the likelihood of fetal mortality by fivefold over that of patients without either risk factor. Maternal hemodynamic parameters did not predict fetal loss. Two patients lost their fetuses despite insignificant trauma (ISS = 1) and normal hemodynamic parameters, whereas eight delivered normal babies despite major trauma (ISS > or = 16). Hemodynamic stability on admission does not predict fetal mortality. Although the presence of moderate to severe injuries (ISS > or = 9) increases the likelihood of fetal mortality, this complication may occur even with insignificant trauma. Close maternal and fetal monitoring is justified, regardless of maternal hemodynamic presentation or severity of injury.

Abbreviated Injury Scale↗
PubMed1999

HIV-1 RNA in plasma and genital tract secretions in women infected with HIV-1.

To assess antiretroviral therapy, all compartments, including the genital tract, need to be evaluated. HIV-1 RNA was quantified in whole cervicovaginal lavage fluid (CVL) and plasma of 56 women and in the cellular and supernatant fractions of 27 of these women. Overall, we detected HIV-1 RNA in 59% of whole CVL samples and in 61% and 44% of cellular and supernatant fractions of the subset of women, respectively. Detectability of HIV-1 RNA in CVL increased with increasing level of plasma RNA in both unfractionated and cell-associated CVL components (p = .0004 and .002, respectively), but not in the cell-free fraction (p = .29). Mean HIV-1 RNA levels in CVL increased with decreasing CD4 counts (p = .002,) and with increasing plasma HIV-1 RNA (p < .001). Adjusted odds ratios (OR) for detectable CVL RNA were highest for women with CD4 counts <200 cells/mm3 (OR, 10.1; 95% confidence interval [CI]: 1.6-82.7; p = .02) and >50,000 copies/ml of plasma RNA (OR, 25.2; 95% CI, 3.2-554; p = .01). Treatment did not seem to affect RNA detection in CVL after adjusting for plasma RNA and CD4. In conclusion, we found that detectability and level of CVL RNA were closely associated with the cellular fraction of genital secretions in women and strongly correlated with the level of plasma RNA and CD4. Genital tract secretions may need to be tested in the assessment of treatment efficacy and this can easily be accomplished with this rapid and easy procedure using whole CVL.

CD4 Lymphocyte Count↗