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Biomedical subjects

L S Chan

Publications and source records attributed to L S Chan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cerebral vasculopathy in sickle cell anemia: diagnostic contribution of positron emission tomography.

Children with sickle cell anemia (SS) have an increased risk for cerebral vasculopathy with stroke (CVA) and cognitive impairment. The present study examines the extent to which adding positron emission tomography (PET) to magnetic resonance imaging (MRI) can improve the detection of cerebral vasculopathy. Whereas MRI has been the prime modality for showing anatomical lesions, PET excels at assessing the functional metabolic state through glucose utilization 2-deoxy-2 [18F] fluoro-D-glucose (FDG) and microvascular blood flow ([15O]H2O). Forty-nine SS children were studied. Among them, 19 had clinically overt CVA, 20 had life-threatening hypoxic episodes or soft neurologic signs, and 10 were normal based on neurological history and examination. For the entire sample of 49 subjects, 30 (61%) had abnormal MRI findings, 36 (73%) had abnormal PET findings, and 44 (90%) showed abnormalities on either the MRI or the PET or both. Of the 19 subjects with overt CVA, 17 had abnormal MRI (89%), 17 had abnormal PET (89%), and 19 (100%) had either abnormal MRI or PET or both. Among the 20 subjects with soft neurologic signs, 10 (50%) had abnormal MRI, 13 (65%) had abnormal PET, and 17 (85%) had abnormal MRI and/or PET. Six (60%) of the 10 neurologically normal subjects had abnormal PET. Among the 30 subjects with no overt CVA, 25 (83%) demonstrated imaging abnormalities based on either MRI or PET or both, thus, silent ischemia. Lower than average full-scale intelligence quotient (FSIQ) was associated with either overt CVA or silent ischemic lesions. Four subjects who received chronic red blood cell transfusion showed improved metabolic and perfusion status on repeat PET scans. In conclusion, (1) the addition of PET to MRI identified a much greater proportion of SS children with neuroimaging abnormalities, particularly in those who had no history of overt neurologic events. (2) PET lesions are more extensive, often bihemispheric, as compared with MRI abnormalities. (3) PET may be useful in management as a tool to evaluate metabolic improvement after therapeutic interventions, and (4) the correlation of PET abnormalities to subsequent stroke or progressive neurologic dysfunction requires further study.

Adolescent↗
PubMed1999

Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6, and type VII collagen.

BACKGROUND: Bullous systemic lupus erythematosus is a generalized subepidermal blistering skin eruption in patients suffering from systemic lupus erythematosus. Type VII collagen was initially identified as the target antigen. OBSERVATION: We studied an unusual patient who had bullous systemic lupus crythematosus. The patient fulfilled the criteria of systemic lupus with an antinuclear antibody titer of 1:5120. Immunopathological testing revealed in vivo deposition of all IgG subclasses, secretory IgA1, and both light chains at the patient's skin basement membrane. The in vivo-bound IgG and IgA were localized at the hemidesmosomes and lamina densa. The patient's IgG and IgA circulating autoantibodies labeled both the epidermal roof and the dermal floor of salt-split skin and recognized the hemidesmosomal protein BP230 as well as the full-length native form and the recombinant noncollagenous domain 1 of type VII collagen (anchoring fibril). In addition, the patient's IgG autoantibodies recognized the anchoring filament proteins laminin-5 and laminin-6 (alpha3 chain and gamma2 chain). CONCLUSIONS: We conclude that patients with bullous systemic lupus erythematosus may have autoantibodies to multiple basement membrane components critical for epidermal-dermal junctional adhesion. Possible pathogenic mechanisms in this patient's clinical diseases include provocation of organ-specific disease (bullous disease) by systemic autoimmunity (lupus) and the "epitope spreading" immune phenomenon.

Adolescent↗
PubMed1999

The new pemphigus variants.

Pemphigus describes a group of autoimmune diseases characterized by blisters and erosions of the skin and mucous membranes, acantholysis by histology, and autoantibodies directed against epidermal cell surface components. Since the early 1970s, the following new clinical variants of pemphigus have been reported: pemphigus herpetiformis, IgA pemphigus, and paraneoplastic pemphigus. In recent years, significant data have been obtained from laboratory investigation on these rare and atypical variants, especially regarding their specific target antigens. We review these variants, their clinical presentations, histologic findings, immunopathology, target antigens, theories of pathogenesis, treatment modalities, and clinical courses.

Acantholysis↗
PubMed1999

Use of heliox-driven nebulizer therapy in the treatment of acute asthma.

STUDY OBJECTIVE: To compare the effectiveness of a helium-oxygen mixture with that of oxygen alone as an aerosolizing gas for beta-agonist therapy in patients with mild to moderate exacerbation of asthma. METHODS: A prospective, single-blinded study was performed in an urban teaching hospital over a period of 5 months. A convenience sample of 205 patients with mild to moderate exacerbation of asthma were enrolled. The participants were randomly assigned to 1 of 2 groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of oxygen, 15 minutes apart. The second group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1 ) were measured before and after each treatment. Only PEFR and FEV1 were used in data analysis. RESULTS: Although both the heliox and the oxygen group showed significant improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively), the difference between the 2 groups was clinically and statistically insignificant (P =.56). Similar findings were observed for FEV1. There was no difference in rate of admission or rate of complications between the 2 groups. CONCLUSION: Despite its ability to decrease the turbulent flow in airways and to reach distal pulmonary tissues, heliox had no clinically significant advantage over standard therapy in the treatment of mild to moderate asthma. Further large-scale studies are necessary to determine the clinical efficacy of heliox in this setting.

Adolescent↗
PubMed1999

Complementary peptides against the major epitope in the NC16A domain of BP180 show no specificity as vaccines to bullous pemphigoid.

A stretch of 14 amino acids (542-555) (MCW-1) in the NC16A domain of BP180 has been shown to be an immunogenic and pathogenic epitope for bullous pemphigoid (BP). Therefore, it provides an excellent target for treatment through a complementary peptide approach, which has been established in other autoimmune diseases, including experimental autoimmune myasthenia gravis. We examined two synthetic complementary peptides BP3CP5 and BP5CP3 against this region. These peptides were derived, respectively, by reading the antisense RNA of this region of BP180 in 3'-5' and 5'-3' directions. We found evident complementarities in hydropathic scores between MCW-1 and both complementary peptides. However, by enzyme-linked immunosorbent assay (ELISA), the complementary peptides BP3CP5 and BP5CP3 did not bind to either synthetic peptide BPNP or glutathione-S-transferase (GST) fusion proteins BP180NC16a and GST-BP-1050. BPNP, BP180NC16a and GST-BP-1050 cover the MCW-1 region of BP180 and were used as the natural peptides in this study. In addition, neither BP3CP5 nor BP5CP3 blocked the reaction between BPNP and anti-BPNP antibody, nor did they block immunofluorescent staining of the basement membrane zone by BP sera. Pre-incubation with BP3CP5 and BP5CP3 did not block the binding of BP sera to the BP18NC16a fusion protein in immunoblotting. Furthermore, rabbit antisera raised against BP3CP5 and BP5CP3 did not bind BP sera in ELISA. Pre-incubation with these rabbit antisera did not inhibit or reduce the binding of BP sera to the autoanltigen in either imnmunoblotting or immunofluorescence. Thus, we concluded that complementary peptides against this particular epitope in BP180 NC16A domain showed no specificity as vaccines to BP, although this approach should be tried for other epitopes in various autoimmune bullous diseases.

Animals↗
PubMed1999

Netilmicin pharmacokinetics in Hong Kong Chinese cancer patients.

OBJECTIVES: To study the pharmacokinetics of netilmicin in Chinese haematology-oncology patients and to determine the pharmacokinetic differences, if any, between this patient subpopulation of Chinese and Caucasians. METHODS: A prospective study was carried out in the adult oncology unit of a major hospital in Hong Kong. During a 6 week period in 1997, all patients commencing on netilmicin therapy were monitored; the patients' demographics, clinical status, netilmicin dose and regimen, and drug administration/blood sampling time were collected. Pharmacokinetic parameters were generated using the USC*PACK package based on specifics of the patients themselves and Caucasians matched for the same patients' parameters using the Bayesian alogrithms. RESULTS: A total of 22 patients were enrolled into the study. Twenty-nine sets of levels were drawn, but only 25 sets from 18 patients (86%) were interpretable. The predicted peak (7.47+/-1.46 microg ml-1 ) and trough levels (1.39+/-0.96 microg ml-1 ) generated by USC*PACK were found to be significantly higher than the levels observed (6.01+/-1.14 microg ml-1 and 0.93+/-0.71 microg ml-1, respectively). Netilmicin clearance, volume of distribution and rate of elimination were all significantly higher in this Chinese subpopulation than those predicted for matched Caucasians. Conclusion Alterations in the netilmicin pharmacokinetics observed in our study population might be related to the disease state and/or ethics of the study patient population. Direct application of Caucasian based population pharmacokinetic parameters to this subgroup of Chinese patients may not be appropriate and may result in underdose.

Adolescent↗
PubMed1999

Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

Animals↗
PubMed1999

High-frequency percussive ventilation improves oxygenation in patients with ARDS.

STUDY OBJECTIVES: To evaluate changes in respiratory and hemodynamic function of patients with ARDS and requiring high-frequency percussive ventilation (HFPV) after failure of conventional ventilation (CV). DESIGN: Retrospective case series. SETTING: Surgical ICU (SICU) and medical ICU (MICU) of an academic county facility. MEASUREMENTS AND RESULTS: Thirty-two consecutive patients with ARDS (20 from SICU, 12 from MICU) who were unresponsive to at least 48 h of CV and were switched to HFPV were studied. Data on respiratory and hemodynamic parameters were collected during the 48 h preceding and the 48 h after institution of HFPV and compared. Between the period of CV and the period of HFPV, the ratio of PaO2 to the fraction of inspired oxygen (F(IO2)) increased ([mean+/-SE] 130+/-8 vs. 172+/-17; p = 0.027), peak inspiratory pressure (PIP) decreased (39.5+/-1.7 vs. 32.5+/-1.9 mm Hg; p = 0.002), and mean airway pressure(MAP) increased (19.2+/-1.2 vs. 27.5+/-1.4 mm Hg; p<0.001). The rate of change of PaO2/F(IO2) per hour was also significantly improved between the two periods. The same changes in PaO2/F(IO2), PIP, and MAP were observed when the last value recorded while the patients were on CV was compared with the first value recorded after 1 h of HFPV. This improvement was sustained but not amplified during the hours of HFPV. The patterns of improvement in these three parameters were similar in SICU and MICU patients as well as in volume-control and pressure-control patients. There were no changes in hemodynamic parameters. CONCLUSION: The HFPV improves oxygenation by increasing MAP and decreasing PIP. This improvement is achieved soon after institution of HFPV and is maintained without affecting hemodynamics.

Adult↗
PubMed1999

Complex repair for the management of duodenal injuries.

The management of duodenal injuries is a subject of ongoing debate. In this study we attempt to describe duodenum-related morbidity (DRM) after primary repair or complex repair (CR) and to identify risk factors for development of complications. The medical records of 145 consecutive patients admitted to Los Angeles County + University of Southern California Medical Center with duodenal injuries between January 1991 and December 1997 were reviewed. Fifty-four (37%) died within 24 hours of admission because of associated injuries. The remaining 91 were subjected to univariate and multivariate analysis. Of them, 66 (72.5%) developed complications and 3 (3%) died. CR was used in 32 (35%) patients and with increasing frequency as the grade of duodenal injury increased. DRM rate was overall low (9%) and not different between low-grade and high-grade duodenal injuries. This occurred despite a significant increase in Injury Severity Score and abdominal Abbreviated Injury Score in patients with more severe duodenal injuries. Patients with overall complications had higher Injury Severity Scores, higher abdominal Abbreviated Injury Scores, and more severe duodenal injuries. We conclude that duodenal injuries are frequently associated with other highly lethal injuries. Liberal use of CR in patients with more severe duodenal injuries prevents DRM.

Abdominal Injuries↗
PubMed1998

Molecular cloning and characterization of a cDNA encoding canine type VII collagen non-collagenous (NC1) domain, the target antigen of autoimmune disease epidermolysis bullosa acquisita (EBA).

Type VII collagen, the major component of anchoring fibrils, serves as tight adhesion of skin basement membrane zone (BMZ) through its amino-terminal non-collagenous (NC1) domain. The NC1 domain is targeted by autoantibodies of an acquired blistering skin disease termed epidermolysis bullosa acquisita (EBA) naturally occurring in humans and dogs. We cloned the full-length canine type VII collagen NC1 domain cDNA and delineated its molecular and immunological characteristics. The canine NC1 domain cDNA consists of 3759 nucleotides encoding for 1253 amino acids, with a molecular mass of approx. 134 kDa and a 17 amino acid signal peptide. The expression of canine type VII collagen was confirmed by Northern blot analysis and by a rabbit antibody raised against a 17 amino acid peptide deduced from canine NC1 sequence. Comparison of canine NC1 with the corresponding human sequence indicated 86.7% and 87.6% identity at the nucleotide and deduced amino acid levels respectively. The protein homology reached greater than 95% within two immunodominant epitope areas. Furthermore, human EBA autoantibodies and a rabbit anti-human NC1 cross-reacted with canine skin BMZ and the newly synthesized canine type VII collagen. The molecular and immunological identities between human and canine NC1 domains suggest that NC1 may be critical for the EBA development.

Amino Acid Sequence↗
PubMed1998

Maternal and infant complications in high and normal weight infants by method of delivery.

OBJECTIVE: To estimate the population risks of maternal and infant complications with the birth of macrosomic (at least 4000 g) compared with normal weight infants. METHODS: Term, singleton infants were identified from the state of Washington's birth event records database for 1990. Diagnosis codes from the Internal Classification of Diseases (9th revision) were used to identify delivery method and previously defined complications. We adjusted for maternal demographic and clinical factors using multivariable logistic regression to derive the risk of each maternal and infant complication. RESULTS: The incidence of macrosomia was 13% (8815 of 66,086). Vaginal birth of macrosomic infants was associated with low incidence of complications except for shoulder dystocia (11%) and postpartum hemorrhage (5%). Postpartum infection was the most common complication for women who had cesarean delivery after labor (5%), and complications for women who had cesarean without labor were rare (less than 3%). Neonatal complications were rare. Among infants with shoulder dystocia, the risks of asphyxia (adjusted relative risk [RR] 1.2, 95% confidence interval [CI] 0.6, 2.3), birth trauma (RR 0.6, 95% CI 0.2, 1.6), long-bone injury (RR 1.2, 95% CI 0.6, 2.4), seizures (RR 1.0, 95% CI 0.0, 25.0), and facial palsy (RR 2.2, 95% CI 0.2, 44.4) were not significantly different for macrosomic and normal weight infants; however, macrosomic infants had a significantly increased risk of Erb palsy (RR 3.5, 95% CI 1.8, 7.5). CONCLUSION: This population-based study showed that most macrosomic infants are delivered vaginally with low rates of maternal and neonatal complications. Macrosomic infants have higher rates of Erb palsy, but similar rates of other serious complications of shoulder dystocia when compared with normal weight infants.

Adult↗
PubMed1998

Partial albinism with immunodeficiency: Griscelli syndrome: report of a case and review of the literature.

Partial albinism with immunodeficiency (Griscelli syndrome) is an uncommon disorder characterized by pigmentary dilution and variable immunodeficiency. Features include a silvery-gray sheen to the hair, large clumped melanosomes in hair shafts, and prominent mature melanosomes in cutaneous melanocytes with sparse pigmentation of adjacent keratinocytes. Immunologic abnormalities most often include impaired natural killer cell activity, absent delayed-type hypersensitivity, and impaired responses to mitogens. Impaired helper T cell function and hypogammaglobulinemia have also been described. The syndrome can be differentiated from Chediak-Higashi syndrome by pathognomonic light and electron microscopic features in skin and hair, and absence of consistent granulocyte abnormalities, but similarly carries a poor prognosis without bone marrow transplantation. We describe a patient with Griscelli syndrome who presented with hepatosplenomegaly, hepatitis, pancytopenia, and silvery hair in the newborn period.

Albinism↗
PubMed1998

Risk factors for early infection of central venous catheters in pediatric patients.

BACKGROUND: In an effort to avoid infections that can lead to the premature removal of indwelling central venous catheters (CVCs), the surgical technique and host factors present in pediatric recipients of permanent CVCs were reviewed. STUDY DESIGN: All patients receiving CVCs over a 17-month period were identified. Those patients with fever and positive blood cultures drawn through the CVC within 45 days of line placement were labeled as having early infection. A case-control design was used to select two control patients for each infected patient. Charts from both the infection and control groups were reviewed for several factors present at the time of CVC placement, including fever, neutropenia (absolute neutrophil count [ANC] < 500 and ANC < 1,000), use of perioperative antibiotics, diagnosis, CVC site, and type of CVC. Chi-square test with Yates correction was used to compare the groups. Odds ratios (ORs) and 95% confidence intervals were derived. RESULTS: Among the 473 CVCs placed, early infections developed in 53 patients (12%). The control group consisted of 106 patients. Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p = 0.004, OR = 5.30). Perioperative antibiotics were given to 25 of 53 infected patients versus 72 of 106 controls (p = 0.02, OR = 0.42). Fever was present in 12 of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92). Factors that were equally prevalent between the groups and that did not appear to influence the CVC infection rate included a diagnosis of malignancy, CVC type, and site of placement. Of the 53 infected catheters, 16 (30%) could not be cleared of infection and were removed. CONCLUSIONS: This study documents that neutropenia and failure to administer prophylactic antibiotics are risk factors for the development of early CVC infection in pediatric patients. To avoid early infection and possible premature CVC removal, we recommend that placement of permanent CVCs be postponed until the ANC is > 1,000. Perioperative antibiotics should be given. A trend toward higher infection rates was seen in patients with preoperative fever.

Adolescent↗
PubMed1998

Sporadic dystrophic epidermolysis bullosa with concomitant atopic dermatitis.

We describe a patient with sporadic dystrophic epidermolysis bullosa associated with well-documented atopic dermatitis. We discuss this case in relation to a newly described clinical subtype of epidermolysis bullosa known as epidermolysis bullosa pruriginosa, a dystrophic variant associated with prominent pruritus. The relations of this case of sporadic dystrophic epidermolysis bullosa with other dominantly inherited forms of dystrophic epidermolysis bullosa such as the Pasini variant, the pretibial variant, and Bart's syndrome are also discussed. The role of atopic dermatitis in exacerbating dystrophic epidermolysis bullosa in this patient raises an important consideration in the care of this group of patients.

Adult↗
PubMed1998

Preferential activation of the complement system in the lower epidermis of patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is an immune-mediated blistering skin disease characterized by acantholysis of the suprabasal epidermis and by IgG autoantibodies targeting a desmosomal component, desmoglein 3. IgG alone has been demonstrated to induce acantholysis in some experimental conditions. The role of the complement system in blister formation in PV remains controversial. We describe four consecutive patients with new-onset PV. The acantholytic process occurred in the lower epidermis and colocalized with deposition of complement C3 and the membrane attack complex C5b-9. The colocalization of complement deposition with the acantholytic process in the lower epidermis supports a role for the complement system in blister formation in PV.

Adult↗
PubMed1998

TRISS methodology in trauma: the need for alternatives.

BACKGROUND: Trauma and Injury Severity Score (TRISS) methodology has become a standard tool for evaluating the performance of trauma centres and identifying cases for critical review. Recent work has identified several limitations and questioned the validity of the methodology in certain types of trauma. METHODS: The usefulness and limitations of the TRISS methodology were evaluated in an urban trauma centre. Trauma registry data of 5445 patients with major trauma were analysed with respect to 30 demographic, prehospital, injury severity and hospitalization attributes. The performance of TRISS was measured primarily by the percentage of misclassifications, including false positives and false negatives, comparing the survival status predicted by TRISS with the true status. Sensitivity, specificity, and positive and negative predictive values were also measured for subgroups defined by the 30 attributes. Logistic regression analysis was used to identify significant independent factors related to the performance of TRISS. RESULTS: The overall misclassification rate was 4.3 per cent. However, in many subgroups of patients with severe trauma the misclassification rate was very high: 34 per cent in patients older than 54 years with Injury Severity Score (ISS) greater than 20; 29 per cent in those with fall injuries and ISS above 20; 29 per cent in patients with injuries involving four or more body areas and ISS greater than 20; 28.6 per cent in patients with injuries needing admission to the intensive care unit (ICU) and ISS greater than 20; 26.4 per cent in patients in severe distress before reaching hospital with ISS greater than 20; and 26.1 per cent in patients whose ISS score was above 20 and who had complications in hospital. CONCLUSION: The TRISS methodology has major limitations in many subgroups of patients, especially in severe trauma. In its present form TRISS has no useful role in major urban trauma centres. Its use should be seriously reconsidered, if not abandoned.

Aged↗
PubMed1998

Epitope spreading: lessons from autoimmune skin diseases.

Autoimmune diseases are initiated when patients develop aberrant T and/or B cell responses against self proteins. These responses presumably are directed to single immunogenic epitopes on these proteins. Recent data in animal models of autoimmune diseases suggest that the targets of immune responses in autoimmunity do not remain fixed, but can be extended to include other epitopes on the same protein or other proteins in the same tissue, a phenomenon termed "epitope spreading." The "epitope spreading" phenomenon also applies to situations in which tissue damage from a primary inflammatory process causes the release and exposure of a previously "sequestered" antigen, leading to a secondary autoimmune response against the newly released antigen. In experimental autoimmune animal diseases, "epitope spreading" seems to have significant physiologic importance in determining the course and duration of disease. In this paper, we review the current concepts in animal models of autoimmune diseases in order to define the "epitope spreading" phenomenon, and we then propose how this phenomenon might play a significant role in the development and the course of autoimmune skin diseases. Hopefully, an understanding of "epitope spreading" will help the dermatology community to better understand the pathogenesis of autoimmune skin diseases and to rationally fashion disease-specific immune therapy in the future.

Animals↗