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Biomedical subjects

D Lynch

Publications and source records attributed to D Lynch.

At least 37 records · Page 2Linked to original sources
PubMed1999

A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.

Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.

Acetic Acid↗
PubMed1999

Right ventricular phenotypic characteristics in subjects with primary pulmonary hypertension or idiopathic dilated cardiomyopathy.

BACKGROUND: Studies of animal models and human subjects with cardiomyopathies suggest that cardiac myocyte and ventricular chamber remodeling show distinct phenotypic characteristics that may be dependent on specific signaling pathways. METHODS AND RESULTS: In this study, we characterize right ventricular (RV) chamber size, end-diastolic thickness, myocardial mass, and ejection fraction (EF) in human subjects with chronic heart failure from primary pulmonary hypertension (PPH; n = 10) and idiopathic dilated cardiomyopathy (IDC; n = 10). Subjects underwent gated cardiac magnetic resonance imaging (MRI), and the RVs were phenotypically classified based on the presence or absence of hypertrophy (increased mass), systolic dysfunction (reduced EF), and degree of wall thickness (concentric v eccentric pattern of hypertrophy). Within this schema, five abnormal phenotypes could be identified. In PPH subjects, in whom the RV is subjected to the uniform insult of chronic pressure overload, four different abnormal phenotypes were identified. CONCLUSIONS: These data indicate that distinct structural/functional ventricular chamber phenotypes may be classified by MRI, and that a uniform insult can result in multiple RV phenotypes.

Cardiomyopathy, Dilated↗
PubMed1999

Invasion by esophageal cancer cells: functional contribution of the urokinase plasminogen activation system, and inhibition by antisense oligonucleotides to urokinase or urokinase receptor.

Early metastasis contributes to the very poor prognosis of esophageal carcinoma. The recent immunohistochemical finding that invasive esophageal carcinomas express elevated levels of urokinase (uPA) and urokinase receptor (uPA-R) in vivo suggest that the plasminogen activation system may contribute to metastasis in esophageal cancer. The aim of our study was to functionally investigate, at the molecular level, the relative contribution of uPA and uPA-R to the invasiveness of esophageal cancer cells in vitro. The three esophageal cancer cell lines, OC1-3, generated in our laboratory, were analyzed for uPA and uPA-R expression by RT-PCR, immunoenzymatic staining, and quantitative ELISA. Invasiveness of all cell lines was quantified as percentage cellular invasiveness in a standardized Matrigel in vitro assay. OC1 and OC3, which were found to coexpress both uPA and uPA-R, displayed stronger invasiveness (44% and 32.5% respectively) relative to OC2 (19%) which expressed uPA-R but was negative for uPA. Transfection of OC2 cells with the uPA cDNA resulted in two variants, OC2.uPA1 and OC2.uPA2, stably expressing functional uPA. Both transfectants exhibited enhanced invasiveness (60% and 50% respectively) relative to the parent uPA-negative OC2 cells (19%). Antisense oligonucleotide inhibition of either uPA or uPA-R expression resulted in a similar, marked reduction in invasiveness of esophageal tumor cells which normally coexpress both molecules (OC1, OC3 and the uPA-expressing OC2-transfectant clones). Neither antisense treatment altered the basal invasiveness of OC2, which expresses uPA-R but not uPA. In conclusion, coexpression of uPA with its receptor, uPA-R, is required for functional involvement of the urokinase system in invasion by esophageal carcinoma cells. Our results suggest that these synergistic mediators of invasiveness are quantitatively major contributors to the invasiveness of esophageal carcinoma.

DNA, Complementary↗
PubMed1999

Application of the high risk model of threat perception to a primary care patient population.

This study was designed to test the hypothesis that patients with a tendency to somatize psychological distress into physical symptoms could be differentiated from patients who do not somatize on the basis of specific predisposing factors defined by the High Risk Model of Threat Perception. Patients in a family practice were assessed for the tendency to somatize by the Diagnostic Interview Schedule (DIS) and by physician rating. Twenty-seven percent of the patients were positive for tendency to somatize by physician rating. These patients had relatively high negative affect, absorption, catastrophizing, self-reported pain and stress, and greater utilization of services. None of the patients assessed by the DIS met criteria for somatization disorder, but 28% were positive for somatoform pain disorder. These patients also scored higher on the negative affect questionnaire, tended to have higher absorption scores, reported greater pain and stress, and utilized more services. Results of this study are partially supportive of the High Risk Model of Threat Perception, because two of the predisposer factors were associated both with tendency to somatize by physician rating and with somatoform pain disorder by interview. The higher utilization of services in the somatizing patients has cost and service ramifications. Treatment of patients with tendencies to somatize within a family practice setting are discussed.

Causality↗
PubMed1999

Complement-mediated regulation of Trichomonas vaginalis infection in mice.

Trichomonas vaginalis is a flagellated protozoan which causes trichomoniasis, a sexually transmitted disease of the human genitourinary tract. The importance of the alternative complement pathway in host defence against T. vaginalis was investigated in vitro. Kinetic studies utilising immunofixation following electrophoresis showed that both a strongly and weakly virulent strain of T. vaginalis activated murine serum C3. In vivo studies with congenic-resistant, C5-deficient, B10.D2/OSn- and C5-sufficient, B10.D2/nSn mice showed that the presence of C5 is a significant factor in the innate host resistance to primary infection with a strongly virulent, but not a weakly virulent trichomonad strain.

Abscess↗
PubMed1999

Evaluation of the opioid addiction test in an out-patient drug dependency unit.

BACKGROUND: The opioid addiction test is based on the measurement of pupil dilatation in opioid-dependent people in response to conjunctivally applied naloxone hydrochloride. A positive response (pupil dilatation) indicates that the subject is dependent on opioids. AIMS: To evaluate the test in an out-patient setting and to identify factors affecting its outcome. METHOD: Pupil size was measured using binocular pupillometry in 100 new patients attending an out-patient clinic for assessment and treatment of opioid use. Measurement was repeated 40 minutes after the unilateral instillation of naloxone drops into the conjunctival sac. RESULTS: We performed 127 tests, of which 103 (81.1%) were positive. Males, and those not on methadone at the time of the test, were more likely to have a negative test result. CONCLUSIONS: The opioid addiction test proved to be a very useful tool for the rapid diagnosis of opioid dependence in the out-patient clinic. Specialist pupillometric equipment increases the number of patients correctly identified as opioid-dependent on the first visit, but is not essential.

Adolescent↗
PubMed1998

Polymicrogyria in chromosome 22 delection syndrome.

We report two children with chromosome 22q11 deletion syndrome who had neuroradiologic evidence of polymicrogyria. The diagnosis of chromosome 22q11 deletion should be considered in individuals with polymicrogyria.

Brain↗
PubMed1998

Rapid, automated assay for progesterone on the Abbott AxSYM analyzer.

We describe an automated assay for progesterone (P4) in human serum and plasma with the Abbott AxSYM random-access immunoassay analyzer. In this one-step competitive assay, P4 immobilized onto latex microparticles competes with sample P4 for binding to a conjugate of alkaline phosphatase (AP) and anti-P4 antibody. Total CVs ranged from 3.4% to 8.2% in multiple precision studies conducted according to the 20-day NCCLS EP5-T protocol. The detection limit (zero calibrator + 2 SD) was 0.10 microg/L across 36 experiments. Values for diluted samples were 83-116% of expected. Recovery of P4 added to serum specimens was 92-115%. Cross-reactivities with 43 natural and synthetic steroids were 0-6.3%. No significant interference was detected from bilirubin, protein, erythrocytes, hemoglobin, triglycerides, or cholesterol. In a multisite correlation study, AxSYM P4 results compared well with results from a commercial RIA method (n = 1156; r = 0.976; slope = 1.03; y-intercept = 0.04). Assay throughput is >80 tests per hour in batch mode, 60 tests per hour with mixed load list configurations.

Autoanalysis↗
PubMed1998

Validity of the medical outcomes study depression screener in family practice training centers and community settings.

BACKGROUND AND OBJECTIVES: Screening inventories that identify primary care patients suffering from depression should be brief, correlate with depression diagnoses, and be evaluated in populations with whom the inventories will be used. METHODS: A total of 566 patients from a medical school training center and 457 patients from six community family practice offices completed the Medical Outcomes Study (MOS) depression screener and a questionnaire reporting demographic information and health habits. All subjects scoring above the recommended screener cut-off, and a random sample of those scoring below, were interviewed with the Diagnostic Interview Schedule (DIS). RESULTS: A total of 195 subjects from the training center and 147 from the community sample were called and administered the DIS. About 33% of the training center and 25% of the community sample scored above the cutoff. Of those above the cutoff and administered the DIS, 23% of the training center and 10% of the community sample were diagnosed with either major depression or dysthymia. CONCLUSIONS: The MOS screener was an effective method of identifying depressed subjects in the training center and community settings. However, because of the relatively low prevalence of depression in these settings, a relatively high number are falsely screened positive. Identifying these patients as having subthreshold depressive symptoms and the necessity/efficacy of treatment is controversial, as is the use of screening instruments. The simplified MOS scoring strategy and template used in this study would probably increase its usefulness in the primary care setting.

Chi-Square Distribution↗
PubMed1997

Skin carcinogenicity of condensed asphalt roofing fumes and their fractions following dermal application to mice.

Condensed roofing asphalt fumes, generated at 316 degrees C, were collected by cold trap condensation and fractionated by preparative high performance liquid chromatography. Chemical classes in each of the fractions (A-E) were identified by gas chromatography/mass spectroscopy. The fractions, various combinations of fractions, the raw and heated asphalt, the neat asphalt fume and the reconstituted asphalt were tested for carcinogenicity, and three fractions were tested for cocarcinogenicity and tumor promotion with benzo[a]pyrene (BaP). The skin application carcinogenesis bioassay was conducted by twice weekly application of test materials in 0.05 ml of acetone/cyclohexane (1:1) for 104 weeks to 40 groups of male C3H/HeJ mice (30/group). Fractions were applied at a mass in proportion to their amount in the neat asphalt fumes. In addition, the neat asphalt fume was tested on Sencar mice to determine if this strain was more susceptible to the carcinogenic effects of the fumes. Condensed neat asphalt fumes produced similar and statistically significant increased tumor yields of papillomas and carcinomas in both strains as compared to respective vehicle controls. Recombination of all fractions resulted in a tumor response similar to neat asphalt fumes. Among individual fractions, C was most potent, followed by B. The other single fractions were without significant tumorigenic activity. Combinations containing fractions B and C were most active among the mixtures that were assayed and no evidence of enhancement of tumorigenesis in the mixtures was found. No significant cocarcinogenic or tumor promoting activity was observed with fractions A, D, or E and BaP. Raw unheated asphalt produced a few tumors in C3H mice, but no tumors were seen when raw asphalt heated to 316 degrees C, with the fumes permitted to escape, was applied.

Animals↗
PubMed1997

Structure-function studies of interleukin 15 using site-specific mutagenesis, polyethylene glycol conjugation, and homology modeling.

Interleukin (IL)-15 is a multifunctional cytokine that shares many biological activities with IL-2. This functional overlap, as well as receptor binding subunits shared by IL-15 and IL-2, suggests tertiary structural similarities between these two cytokines. In this study, recombinant human IL-15 was PEGylated via lysine-specific conjugation chemistry in order to extend the circulation half-life of this cytokine. Although PEGylation did extend the beta-elimination circulation half-life of IL-15 by greater than 50-fold, the biological activity of polyethylene glycol (PEG)-IL-15 was significantly altered. Specifically, PEG-IL-15 lost its ability to stimulate the proliferation of CTLL but took on the properties of a specific IL-15 antagonist in vitro. In comparing sequence alignments and molecular models for IL-2 and IL-15, it was noted that lysine residues resided in regions of IL-15 that may have selectively disrupted receptor subunit binding. We hypothesized that PEGylation of IL-15 interferes with beta but not alpha receptor subunit binding, resulting in the IL-15 antagonist activity observed in vitro. The validity of this hypothesis was tested by engineering site-specific mutants of human IL-15 as suggested by the IL-15 model (IL-15D8S and IL-15Q108S block beta and gamma receptor subunit binding, respectively). As with PEG-IL-15, these mutants were unable to stimulate CTLL proliferation but were able to specifically inhibit the proliferation of CTLL in response to unmodified IL-15. These results supported our model of IL-15 and confirmed that interference of beta receptor subunit binding by adjacent PEGylation could be responsible for the altered biological activity observed for PEG-IL-15.

Amino Acid Sequence↗
PubMed1997

The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients.

A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. We have evaluated 181 patients with this deletion. We describe our cohort of patients, how they presented, and what has been learned by having the same subspecialists evaluate all of the children. The results help define the extremely variable phenotype associated with this submicroscopic deletion and will assist clinicians in formulating a management plan based on these findings.

Abnormalities, Multiple↗
PubMed1996

Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis.

The function of the minor subset of T lymphocytes bearing the gamma delta T cell antigen receptor is uncertain. Although some gamma delta T cells react to microbial products, responsiveness has only rarely been demonstrated toward a bacterial antigen from a naturally occurring human infection. Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi. Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes. The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.

Apoptosis↗
PubMed1996

Depressive symptoms: associations with health perceptions and health behaviors.

The association of depressive symptoms with health behaviors and perceptions was determined for 876 patients seeing family physicians. Correlational analyses revealed stress, pain, and overall health status were moderately related to depression for males and females. Smoking was positively related to depressive symptoms in women (r = .19, P < 0.01), and drinking was inversely related to depressive symptoms in men (r = -.16, P < .01). Multiple regression analyses indicated stress, poor health, smoking, and drinking were significant predictors of depressive symptoms in women; stress, poor health, and drinking were significant in men. Health perceptions appear to be better predictors of depressive symptoms than reported health behaviors.

Adolescent↗
PubMed1996

Cystic renal cell carcinoma: radiological features and clinico-pathological correlation.

The radiological appearances of 11 cystic renal cell carcinomas (RCC) presenting over a 13-year-period are reviewed and correlated with their clinicopathological features. The tumours occurred in seven males and four females with a mean age of 59.1 years (range 27-87 years). Their ultrasound features were categorized according to Bosniak [5]. There were six category 3 or 4 cysts (indeterminate or malignant); three category 2 cysts and two category 1 cysts. Computed tomography scans (CT) demonstrated malignant features in all seven patients scanned. Cyst aspiration, intravenous urograms and arteriograms were generally unhelpful. Histological growth patterns of nine tumours were determined and all were staged by Robson's classification: eight were Stage 1, one was Stage 3 and two were Stage 4. Three of four deaths were related to tumour bulk, and the fourth patient died from an unrelated cause. All seven survivors had Stage 1 disease. No correlation existed between different histological subtypes and tumour aggression. Overall, the behaviour of cystic RCCs was similar to those of solid RCCs apart from the high percentage (72.2%) of Stage 1 disease. We conclude that any deviation from a simple cyst on ultrasound should be assessed by CT and/or surgery. Indeterminate lesions on CT including multilocular lesions should be surgically explored.

Adult↗
PubMed1996

Multicenter evaluation of the Abbott IMx CA 15-3 assay.

We describe a new fully automated procedure for the quantitative measurement of CA 15-3: the microparticle enzyme immunoassay (MEIA) technology developed by Abbott Labs. for the IMx automated immunoassay analyzer. The new IMx CA 15-3 test uses two mouse monoclonal antibodies, 115D8 and DF3. The test has a dynamic range to 250 kilounits/L and a minimal detectable dose of CA 15-3 < 0.2 kilounits/L. On dilution, linearity is excellent, with recoveries ranging from 94% to 101%. Studies were conducted at four sites to evaluate the performance characteristics of this assay. The intra- and interassay CVs were < 4.7% and < 5.6%, respectively, and showed a between-laboratory CV < 5.9%. Test results of the Abbott IMx CA 15-3 (y) were correlated with those obtained with the Centocor CA 15-3 RIA (x), a solid-phase heterologous RIA. Linear regression analysis on results for 1973 samples yielded: y = 0.97x - 2.09 (r = 0.9899, Sy/x = 22.2, range 1-4089 kilounits/L).

Animals↗
PubMed1995

Autosomal dominant "Opitz" GBBB syndrome due to a 22q11.2 deletion.

We report on a family with autosomal dominant paternally inherited "Opitz" GBBB syndrome and an additional case with findings which have been reported in that syndrome. In each case the propositus presented with a vascular ring. Since a vascular ring may be a sign of a 22q11.2 deletion [Zacki et al., 1995], FISH (fluorescence in situ hybridization) studies were performed. These studies demonstrated a 22q11.2 deletion in the 3 affected individuals. Review of Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome demonstrates significant overlap of manifestations including both facial characteristics and structural anomalies. Based on the phenotypic overlap and the presence of a 22q11.2 deletion in our patients with Opitz GBBB syndrome and the presence of a deletion in a patient with lung hypoplasia, absent pulmonary artery, and long segment tracheomalacia, we propose that, in some cases, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. This enlarges the list of "syndromes" associated with the 22q11.2 deletion, which presently includes most patients with DiGeorge, velocardiofacial, and conotruncal anomaly face syndrome.

Abnormalities, Multiple↗