Biomedical subjects

Y Chang

Publications and source records attributed to Y Chang.

At least 127 records · Page 7Linked to original sources

PubMed1999

Crosslinking characteristics and mechanical properties of a bovine pericardium fixed with a naturally occurring crosslinking agent.

Currently available crosslinking agents used in fixing bioprostheses are all highly (or relatively highly) cytotoxic, which may induce an adverse inflammatory reaction in vivo. It is therefore desirable to provide a crosslinking agent that is of low cytotoxicty and may form stable and biocompatible crosslinked products. To achieve this goal, a naturally occurring crosslinking agent-genipin-was used by our group to fix biological tissues. Genipin may be obtained from its parent compound, geniposide, which may be isolated from the fruits of Gardenia jasminoides Ellis. In our previous studies, it was found that the cytotoxicity of genipin is significantly lower than both glutaraldehyde and an epoxy compound. Also, it was shown that genipin can form stable and biocompatible crosslinked products. The present study further investigates the crosslinking characteristics and mechanical properties of a genipin-fixed bovine pericardium. Fresh and glutaraldehyde- and epoxy-fixed counterparts were used as controls. It was found that the denaturation temperatures of the glutaraldehyde- and genipin-fixed tissues were significantly greater than the epoxy-fixed tissue, although their fixation indices were comparable. The mechanical properties of fresh bovine pericardium are anisotropic. However, fixation tended to eliminate tissue anisotropy. The tendency in the elimination of tissue anisotropy for the genipin-fixed tissue was more remarkable than for the glutaraldehyde- and epoxy-fixed tissues. In addition, the genipin-fixed tissue had the greatest ultimate tensile strength and toughness among all the fixed tissues. Distinct patterns in rupture were observed in the study: The torn collagen fibers of the genipin- and glutaraldehyde-fixed tissues appeared to be bound together, while those of fresh and the epoxy-fixed tissues stayed loose. The results obtained in the study suggests that tissue fixation in glutaraldehyde, epoxy compound, and genipin may produce distinct crosslinking structures. The differences in crosslinking structure may affect the crosslinking characteristics and mechanical properties of the fixed tissues.

Animals↗

PubMed1999

Predictors of recurrence in surgical stage II endometrial adenocarcinoma.

OBJECTIVE: A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival. METHODS: A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging. Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately. RESULTS: Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2-9.6 years). Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%. The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis. CONCLUSION: This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease. LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified.

Adenocarcinoma↗

PubMed1999

Allosteric activation mechanism of the alpha 1 beta 2 gamma 2 gamma-aminobutyric acid type A receptor revealed by mutation of the conserved M2 leucine.

A conserved leucine residue in the midpoint of the second transmembrane domain (M2) of the ligand-activated ion channel family has been proposed to play an important role in receptor activation. In this study, we assessed the importance of this leucine in the activation of rat alpha 1 beta 2 gamma 2 GABA receptors expressed in Xenopus laevis oocytes by site-directed mutagenesis and two-electrode voltage clamp. The hydrophobic conserved M2 leucines in alpha1(L263), beta2(L259), and gamma 2(L274) subunits were mutated to the hydrophilic amino acid residue serine and coexpressed in all possible combinations with their wild-type and/or mutant counterparts. The mutation in any one subunit decreased the EC(50) and created spontaneous openings that were blocked by picrotoxin and, surprisingly, by the competitive antagonist bicuculline. The magnitudes of the shifts in GABA EC(50) and picrotoxin IC(50) as well as the degree of spontaneous openings were all correlated with the number of subunits carrying the leucine mutation. Simultaneous mutation of the GABA binding site (beta 2Y157S; increased the EC(50)) and the conserved M2 leucine (beta 2L259S; decreased the EC(50)) produced receptors with the predicted intermediate agonist sensitivity, indicating the two mutations affect binding and gating independently. The results are discussed in light of a proposed allosteric activation mechanism.

Allosteric Regulation↗

PubMed1999

Effect of a baseline ovarian cyst on the outcome of in vitro fertilization-embryo transfer.

OBJECTIVE: To determine the significance of prestimulation ovarian cysts on the response to controlled ovarian hyperstimulation and the outcome of IVF. DESIGN: Retrospective study. SETTING: In vitro fertilization unit in an academic center. PATIENT(S): One hundred thirty-seven patients undergoing IVF. INTERVENTION(S): The outcome of 71 patients who had an ovarian cyst of >10 mm detected at ultrasound examination performed on day 3 was compared with that of 66 patients who underwent a similar protocol and did not have an ovarian cyst. MAIN OUTCOME MEASURE(S): Parameters evaluated were the E2 level on the day of hCG administration, the number of follicles, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate. RESULT(S): The E2 level on the day of hCG administration and the number of mature oocytes retrieved were lower in the group with a baseline cyst. The pregnancy rate also was significantly lower in the group with a cyst (24% versus 41%). The presence of a baseline ovarian cyst decreases the odds of pregnancy 0.37-fold (95% confidence interval, 0.16-0.87). CONCLUSION(S): A baseline ovarian cyst on cycle day 3 was associated with a poorer outcome after IVF-ET.

Adult↗

PubMed1999

Mechanical properties of a porcine aortic valve fixed with a naturally occurring crosslinking agent.

The study investigates the mechanical properties of porcine aortic valve leaflets fixed with a naturally occurring crosslinking agent, genipin, at distinct pressure heads. Fresh and the glutaraldehyde-fixed counterparts were used as controls. Subsequent to fixation, the changes in leaflet collagen crimps and its surface morphology were investigated by light microscopy and scanning electron microscopy (SEM). Also, the crosslinking characteristics of each studied group were determined by measuring its fixation index and denaturation temperature. In the mechanical testing, tissue strips made from each studied group were examined in both the circumferential and radial directions. Histological and SEM comparisons between fresh porcine aortic valve leaflet and those fixed at medium or high pressure revealed that the following changes may occur: elimination of the natural collagen crimping, and extensive loss of the endothelial layer. The denaturation temperatures of the glutaraldehyde-fixed leaflets were significantly greater than the genipin-fixed leaflets; however, their fixation indices were comparable. Generally, fixation pressure did not affect the crosslinking characteristics of the genipin- and glutaraldehyde-fixed leaflets. It was found that fixation of porcine aortic valves in genipin or glutaraldehyde did not alter the mechanical anisotropy observed in fresh valve leaflets. This indicated that the intramolecular and intermolecular crosslinks introduced into the collagen fibrils during fixation is of secondary importance to the presence of structural and mechanical anisotropy in fresh leaflet. Tissue fixation in genipin or glutaraldehyde may produce distinct crosslinking structures. However, the difference in crosslinking structure between the genipin- and glutaraldehyde-fixed leaflets did not seem to cause any significant discrepancies in their mechanical properties when compared at the same fixation pressure. Nevertheless, regardless of the crosslinking agent used, changes in mechanical properties and ruptured patterns were observed when the valve leaflets were fixed at distinct pressures.

Animals↗

PubMed1999

KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a structural and functional homologue of human IL-6 called viral IL-6 (vIL-6). Expression of vIL-6 in KSHV-related lymphoproliferative disorders has been implicated in their pathogenesis. vIL-6 has been shown to mimic a number of IL-6 activities including stimulating the growth of IL-6 dependent cell lines and activating the JAK1 and STAT1/3 pathway in HepG2 cells. However, IL-6 and vIL-6 display differences in receptor usage that may give rise to underlying qualitative and quantitative differences in the signaling pathways utilized. While IL-6 has an absolute requirement for both the IL-6 Ralpha and the gp130 subunits, vIL-6 appears to require only gp130. In addition to JAK1 and STAT1/3 pathways, IL-6 activates multiple other pathways including the direct activation of STAT 5 by JAK1, the Ras-MAP kinase cascade and a novel H7-sensitive pathway. In this study we examined whether vIL-6 is capable of signaling via distinct IL-6 response elements (IL-6 RE) under the control of these different pathways. We show that vIL-6 activates both STAT1/3- and STAT5-dependent Type II IL-6 REs. In addition, vIL-6 induces transcriptional activation via a Type I IL-6 RE that binds C/EBP, indicative of Ras-MAP kinase pathway induction. Furthermore, vIL-6 is capable of activating the IL-6 response element in the c-jun promoter (RE-IL-6). vIL-6 induced activation of JRE-IL-6 requires both the Ets- and Cre-like sites, suggesting that vIL-6 is capable of stimulating the same novel serine/threonine kinase mediated pathway as IL-6. These results demonstrate that vIL-6 can stimulate all of the known IL-6-induced signaling pathways. Therefore, vIL-6 could potentially contribute to KSHV-related disease progression by continued activation of IL-6-stimulated growth and anti-apoptotic pathways even when cells attempt to protect themselves from IL-6 over-stimulation by downmodulating their IL-6Ralpha subunits.

CCAAT-Enhancer-Binding Proteins↗

PubMed1999

Nutritional support for burn injuries.

There are approximately 2,000,000 burns each year in the United States that require medical treatment. Fortunately, most of these can be treated on an outpatient basis; however, 100,000 patients are hospitalized yearly. The mortality rate is higher in patients with large burns or smoke inhalation injury or both, or in patients otherwise compromised by age or concomitant disease. Thermal injury leads to suppression of the immune response, and infectious morbidity is common in all burn patients. In addition, the injury and recovery processes are attended by tremendous catabolism of host tissues, leaving patients debilitated and functionally impaired. Medical nutrition therapy plays a key role in the support of the burn patient, supporting the immune system and blunting the hypermetabolic response.

Journal Article↗

PubMed1999

Functional and structural consequences of aromatic residue substitutions within the kringle-2 domain of tissue-type plasminogen activator.

Aromatic amino acid residues within kringle domains play important roles in the structural stability and ligand-binding properties of these protein modules. In previous investigations, it has been demonstrated that the rigidly conserved Trp25 is primarily involved in stabilizing the conformation of the kringle-2 domain of tissue-type plasminogen activator (K2tpA), whereas Trp63, Trp74, and Tyr76 function in omega-amino acid ligand binding, and, to varying extents, in stabilizing the native folding of this kringle module. In the current study, the remaining aromatic residues of K2tPA, viz., Tyr2, Phe3, Tyr9, Tyr35, Tyr52, have been subjected to structure-function analysis via site-directed mutagenesis studies. Ligand binding was not significantly influenced by conservative amino acid mutations at these residues, but a radical mutation at Tyr35 destabilized the interaction of the ligand with the variant kringle. In addition, as reflected in the values of the melting temperatures, changes at Tyr9 and Tyr52 generally destabilized the native structure of K2tPA to a greater extent than changes at Tyr2, Phe3, and Tyr35. Taken together, results to date show that, in concert with predictions from the crystal structure of K2tpA, ligand binding appears to rely most on the integrity of Trp63 and Trp74, and aromaticity at Tyr76. With regard to aromatic amino acids, kringle folding is most dependent on Tyr9, Trp25, Tyr52, Trp63, and Tyr76. As yet, no obvious major roles have been uncovered for Tyr2, Phe3, or Tyr35 in K2tpA.

Amino Acid Substitution↗

PubMed1999

Channel opening locks agonist onto the GABAC receptor.

Determination of the activation mechanism of neurotransmitter-operated ion channels has been hindered by a limited understanding of the relationship between agonist binding and the gating of the integral ion pore. Here we describe a [3H]ligand binding assay that enables us to make repeated binding measurements from the same intact oocyte expressing recombinant human rho 1 GABAC receptors and directly correlate the binding kinetics with electrophysiological measurements. We have determined an association rate for GABA of about 10(5) M-1s-1; this is four orders of magnitude slower than diffusion, indicating GABA has restricted access to its binding site. We also demonstrate that GABA dissociates at two rates. Our data are consistent with the faster rate being the true microscopic dissociation rate of GABA, with the slower rate occurring because the opening of the pore detains agonist release.

Diffusion↗

PubMed1999

Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein.

We report on long-term delivery of an interferon-gamma (IFN gamma) inhibitory protein by intramuscular (i.m.) gene therapy. IFN gamma is a cytokine that plays an important role in many inflammatory disorders, including autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD mice and (in various strains) multiple low-dose streptozotocin (STZ)-induced diabetes (MDSD). By cDNA insertion into plasmid VICAL VR-1255 we constructed an expression vector encoding a soluble IFN gamma receptor/IgG1 heavy chain (all murine) fusion protein (IFN gamma R/IgG1). This protein is secreted as a homodimer and neutralizes IFN gamma in vitro. We show that i.m. injections of this vector as naked DNA in mice results in secretion of IFN gamma R/IgG1, with serum levels exceeding 100 ng/ml for months after treatment. These levels are sufficient to neutralize IFN gamma in vivo, and to prevent either MDSD or cyclophosphamide (CYP)-accelerated diabetes in NOD mice, which are both characterized by systemic release of IFN gamma. In these diseases gene therapy considerably reduces inflammation in the islets of Langerhans (insulitis). Also, circulating IFN gamma R/IgG1 blocked IFN gamma-enhanced nitric oxide production by peritoneal macrophages. The fusion protein is constructed from non-immunogenic self elements, avoiding a neutralizing immune response and making it suitable for prolonged therapy of numerous inflammatory disorders.

Animals↗

PubMed1999

Concomitant positive reactions to allergens in a patch testing standard series from 1988-1997.

BACKGROUND: Patch testing is a useful diagnostic technique in patients with suspected allergic contact dermatitis (ACD). Concomitant reactions may reflect associations between tested allergens. OBJECTIVE: This study was performed to identify positive correlations between reactions to test substances in a standard screening series. The results of patch testing in patients seen from 1988 to 1997 are described. METHODS: Data were collected from chart review for patients who underwent patch testing to the full standard screening series at the Massachusetts General Hospital Contact Dermatitis Clinic. The Fisher exact test was used to evaluate associations between allergens. RESULTS: A total of 927 patients were patch tested to 22 allergens included in a screening tray. The mean age was 43.9 years, and 68.6% were women. Two or more positive reactions occurred in 36.5% of patients. Reactions to 13 pairs of allergens were found to be significantly correlated: balsam of Peru/fragrance mix, carba mix/thiuram mix, carba mix/paraben mix, cobalt chloride/potassium dichromate, cobalt chloride/nickel sulfate, ethylenediamine/neomycin sulfate, formaldehyde/imidazolidinyl urea, formaldehyde/paraben mix, formaldehyde/quaternium-15, imidazolidinyl urea/quaternium-15, neomycin sulfate/potassium dichromate, paraben mix/quaternium-15, and potassium dichromate/thimerosal. CONCLUSION: Concomitant reactions to 13 pairs of allergens in a standard series occurred at a rate greater than would be predicted by chance. Such associations may reflect cross-sensitization or cosensitization.

Adult↗

PubMed1999

Posttransplantation plasmacytic proliferations related to Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV), which was originally detected in Kaposi's sarcoma, also has been found in primary effusion lymphomas (PELs) and some cases of multicentric Castleman's disease. We describe two transplant recipients who developed Kaposi's sarcoma and a spectrum of non-neoplastic lymphoproliferative disorders that show pronounced plasmacytic and plasmacytoid features. The first patient had recurrent pleural effusions and Castleman's disease-like changes in lymph nodes. The second patient had systemic lymphadenopathy and hepatosplenomegaly secondary to diffuse infiltration by polyclonal plasma cells and plasmacytoid B lymphocytes that clinically mimicked Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. In both cases, KSHV DNA was detected by polymerase chain reaction and Southern blotting, and KSHV vIL-6 protein expression was identified in affected tissues by immunohistochemical localization. In contrast, no evidence of KSHV coinfection was detected in any of 31 EBV-related posttransplant lymphoproliferative disorders or 112 non-PEL lymphomas tested. The pathologic findings in these two patients were not representative of malignancy by morphologic, immunophenotypic, or molecular criteria. This study underscores the marked propensity for hematolymphoid proliferations associated with KSHV infections to show plasmacytic features. Additionally, this study describes use of an antibody reactive against KSHV vIL-6 that can readily detect a subpopulation of KSHV-infected hematopoietic cells.

Adult↗

PubMed1999

Requirement for cell-to-cell contact in Epstein-Barr virus infection of nasopharyngeal carcinoma cells and keratinocytes.

Two nasopharyngeal carcinoma (NPC) cell lines and one keratinocyte cell line could be infected with Epstein-Barr virus (EBV) by cocultivation with virus-producing cells but not by cell-free virus. Using porous culture inserts to manipulate the cell-to-cell contact, we demonstrated that contact between EBV donor B cells and EBV recipient epithelial cells was required for the infection. Cell-to-cell contact not only provided a CR2-independent route of infection but also enhanced CR2-mediated infection in a synergistic manner. Activity of two EBV promoters (Cp and Wp) and expression of EBNA2 were detected in the infected population. A small proportion of the infected cells spontaneously entered an EBV lytic state, which could be induced prominently by chemical treatment. This study provides information on how EBV may infect epithelial cells in vivo, such as at the onset of NPC development.

Cell Line↗

PubMed1999

Characterization and cell cycle regulation of the major Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent genes and their promoter.

Retinoblastoma tumor suppressor protein (pRB) inhibition by tumor virus oncoproteins has been attributed to the need for these viruses to promote lytic viral nucleic acid synthesis by unscheduled entry into the S phase of the cell cycle. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a functional cyclin (vCYC) which is expressed during latency and can direct phosphorylation of pRB. We mapped the two major latent transcripts encoding vCYC, latent transcript 1 (LT1) and LT2, by cDNA sequencing, 5' rapid amplification of cDNA ends, and primer extension analyses. Both LT1 and LT2 transcripts are spliced, originate from the same start site, and encode ORF K13 (vFLIP) as well as ORF72 (vCYC). The latency-associated nuclear antigen (LANA, ORF73) is encoded by LT1 but spliced from LT2. While differential expression of the two transcripts was not found, the promoter controlling LT1/LT2 transcription is regulated in a cell cycle-dependent manner. Activities of both KSHV LT1/LT2 and huCYC D1 luciferase promoter reporters transfected into NIH 3T3 cells increase 11- and 4-fold, respectively, after release from cell cycle arrest by serum starvation. Further, vCYC and huCYC D2 mRNA levels are low in naturally infected BCBL-1 cells arrested in late G1 with L-mimosine but increase in parallel during a 24-h period after release from cell cycle arrest. Cell cycle regulation of KSHV vCYC expression mimics cellular D cyclin regulation and may maintain infected cell cycling. This is consistent with an alternative hypothesis that tumor viruses have developed specific responses to innate cellular defenses against latent virus infection that include pRB-induced cell cycle arrest.

3T3 Cells↗

PubMed1999

Septic arthritis versus transient synovitis at MR imaging: preliminary assessment with signal intensity alterations in bone marrow.

PURPOSE: To find any differential magnetic resonance (MR) imaging findings between septic arthritis and transient synovitis in pediatric patients. MATERIALS AND METHODS: The MR imaging findings in nine pediatric patients with septic arthritis and 14 with transient synovitis were retrospectively studied. The diagnoses were made by means of joint aspiration with bacteriologic study, arthrotomy, and clinical evaluation. MR imaging findings were analyzed with emphasis on the grade of joint effusion and alterations in signal intensity in the soft tissue and bone marrow of the affected hip joint. RESULTS: Signal intensity alterations in bone marrow (i.e., low signal intensity on fat-suppressed gadolinium-enhanced T1-weighted spin-echo images and high signal intensity on fat-suppressed T2-weighted fast spin-echo images) were seen in eight of nine patients with septic arthritis. These signal intensity alterations consisted of mild juxtaarticular changes in six patients without osteomyelitis and extensive changes in the femoral head and neck in two patients with coexistent osteomyelitis. Signal intensity alterations in bone marrow were not seen in the 14 patients with transient synovitis. CONCLUSION: Signal intensity alterations in the bone marrow of the affected hip joint are useful in the differentiation of septic arthritis from transient synovitis.

Adolescent↗

PubMed1999

Role for telemedicine in acute stroke. Feasibility and reliability of remote administration of the NIH stroke scale.

BACKGROUND AND PURPOSE: Immediate access to physicians experienced in acute stroke treatment may improve clinical outcomes in patients with acute stroke. Interactive telemedicine can make stroke specialists available to assist in the evaluation of patients at multiple urban or remote rural facilities. We tested whether interrater agreement for the NIH Stroke Scale (NIHSS), a critical component of acute stroke assessment, would persist if performed over a telemedicine link. METHODS: One bedside and 1 remote NIHSS score were independently obtained on each of 20 patients with ischemic stroke. The bedside examination was performed by a stroke neurologist at the patient's bedside. The remote examination was performed by a second stroke neurologist through an interactive high-speed audio-video link, assisted by a nurse at the patient's bedside. Kappa coefficients were calculated for concordance between bedside and remote scores. RESULTS: Remote assessments took slightly longer than bedside assessments (mean 9.70 versus 6.55 minutes, P<0. 001). NIHSS scores ranged from 1 through 24. Based on weighted kappa coefficients, 4 items (orientation, motor arm, motor leg, and neglect) displayed excellent agreement, 6 items (language, dysarthria, sensation, visual fields, facial palsy, and gaze) displayed good agreement, and 2 items (commands and ataxia) displayed poor agreement. Total NIHSS scores obtained by bedside and remote methods were strongly correlated (r=0.97, P<0.001). CONCLUSIONS: The NIH Stroke Scale remains a swift and reliable clinical instrument when used over interactive video. Application of this technology can bring stroke expertise to the bedside, regardless of patient location.

Acute Disease↗

PubMed1999

The tumescent technique: the effect of high tissue pressure and dilute epinephrine on absorption of lidocaine.

Injection of lidocaine into the subcutaneous tissues by the tumescent technique results in a delayed absorption of the local anesthetic and has allowed clinicians to exceed the maximum recommended dose of lidocaine without reported complications. However, little knowledge exists about the mechanisms that permit such high doses of lidocaine to be used safely with this technique. The presence of low concentration epinephrine and the increased tissue pressure resulting from the tumescent injection have both been implicated as important factors, but neither has been studied in patients whose results were not altered by the variability of the suction procedure. The purpose of this work was to determine the effect of tissue pressure during tumescent injection and presence of low concentration epinephrine on the absorption of lidocaine from subcutaneous tissues in human volunteers. Twenty healthy female human volunteers were randomized into four study groups. After body fat measurements, all subjects received an injection of 7 mg/kg of lidocaine into the subcutaneous tissues of both lateral thighs. The injected solution consisted of 0.1% lidocaine and 12.5 meq/liter sodium bicarbonate in normal saline with or without 1:1,000,000 epinephrine. Tissue pressure was recorded during injection using a specially designed double-barreled needle. The time required for injection was also recorded. Subjects in group 1 received lidocaine with epinephrine injected by a high-pressure technique. Group 2 subjects received lidocaine with epinephrine injected by a low-pressure technique. Group 3 subjects received lidocaine without epinephrine injected under high pressure. Group 4 subjects received lidocaine without epinephrine injected under low pressure. Following injection, sequential blood samples were drawn over a 14-hour period, and plasma lidocaine concentrations were determined by gas chromatography. No suction lipectomy was performed. Maximum tissue pressure during injection was 339 +/- 63 mmHg and 27 +/- 9 mmHg using high- and low-pressure techniques, respectively. Addition of 1:1,000,000 epinephrine, regardless of the pressure of injected fluid, significantly delayed the time to peak plasma concentration by over 7 hours. There was no significant difference in the peak plasma concentration of lidocaine among the four groups. Peak plasma concentrations greater than 1 mcg/ml were seen in 11 subjects. Epinephrine (1:1,000,000) significantly delays the absorption of lidocaine administered by the tumescent technique. High pressure generated in the subcutaneous tissues during injection of the solution does not affect lidocaine absorption. The delay in absorption may allow time for some lidocaine to be removed from the tissues by suction lipectomy. In addition, the slow rise to peak lidocaine concentration in the epinephrine groups may allow the development of systemic tolerance to high lidocaine plasma levels.

Absorption↗

PubMed1999

Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases.

OBJECTIVE: Antiphospholipid (aPL) antibodies are present in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) and are associated with recurrent thromboses, thrombocytopenia, and pregnancy losses. The presence of aPL antibodies is routinely tested using a standardized ELISA that utilizes cardiolipin as antigen (aCL ELISA). This test, although sensitive, is frequently positive in patients with nonrelated autoimmune disorders and some infectious diseases, making the test less specific. Thus there is a need for more specific tests for aCL with equivalent sensitivity to the standard assay. We evaluated the diagnostic utility of a new aPL antibody test kit with a unique phospholipid mixture designed to be more specific than the standard anticardiolipin ELISA. METHODS: aPL antibodies (IgG, IgM) were measured by both a standard ELISA and a new ELISA kit (APhL ELISA Kit, Louisville APL Diagnostics, Inc., Louisville, KY, USA) in the baseline serum from patients enrolled in a 5 year inception cohort, prospective study of early rheumatoid diseases: rheumatoid arthritis (N = 70), SLE (70), scleroderma (45), inflammatory myositis (36), and early undifferentiated connective tissue disease (CTD) (165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjogren's syndrome (44) was also defined. Serum from 200 blood donors (BD) served as controls. Patients with known APS (33) and antinuclear cytoplasmic antibody positive renal vasculitis (52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The kit was 90.9% sensitive for detecting APS. Seven patients missed by the kit all had standard aCL values < 40 PL units. Assuming controls do not have APS, the kit was 99.5% specific vs 96.0% for the standard assay. For the patients with CTD, the kit never detected a patient that was not also detected by the standard aCL assay. CONCLUSION: The APhL ELISA Kit appears to be more specific than the standard aCL ELISA without adding potential false positive results. The new test may be useful for followup study for patients found to be aCL positive by standard assays to increase specificity for aCL screening.

Antibodies, Anticardiolipin↗