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Biomedical subjects

A Raymond

Publications and source records attributed to A Raymond.

At least 19 recordsLinked to original sources

[Multi-organ failures during septic shock from Escherichia coli urinary tract infection: catastrophic antiphospholipid syndrome?].

INTRODUCTION: Although the presence of antiphospholipid antibodies is not an uncommon fact during infection, their responsibility in serious manifestations can still be debated and questions the existence of an actual catastrophic antiphospholipid syndrome or multivisceral faintings, triggered by the infection only, since the presence of antiphospholipid antibodies is not pathogenous. CASE: A 68-year-old man presented during an Escherichia coli urinary tract infection a septic shock with renal and cardiac insufficiencies, hepatic cytolysis and cholestasis and disseminated intravascular coagulation. There was a significant titer of antiphospholipid antibodies IgG (50 UGPL/ml) with an antibêta2-glycoprotein-1 positivity. The patient quickly recovered with antibiotherapy and intravenous immunoglobulins. DISCUSSION: Diagnosing the pathogeny of multivisceral faintings is founded of the clinical manifestations published during the catastrophic antiphospholipid syndrome, the evolution and the persistence of post recovery antibodies and the comparison with the visceral bouts that the sepsis exclusively as revealed.

Aged↗

Dendritic-cell-peptide immunization provides immunoprotection against bcr-abl-positive leukemia in mice.

Chronic myelogenous leukemia (CML) is a clonal disorder characterized by proliferation of cells that possess the bcr-abl fusion gene resulting in the production of one of two possible chimeric 210-kDa tyrosine kinase proteins. Since these chimeric proteins are expressed only in leukemic cells they have the potential to serve as tumor-specific antigens for cytotoxic T lymphocytes (CTL). Using the 12B1 murine leukemia cell line, derived by retroviral transformation of BALB/c bone marrow cells with the bcr-abl (b3a2) fusion gene, we have demonstrated that intravenous inoculation of 12B1 cells into BALB/c mice results in a disseminated acute leukemia analogous to human CML in blast crisis. Histological sections of liver and spleen and polymerase chain reaction analysis of peripheral blood, bone marrow, liver, spleen and lymph nodes confirmed the presence of bcr-abl+ leukemia cells in these murine tissues, while Western blot data demonstrated the expression of the fusion protein in 12B1 cells. Immunization of mice with dendritic cells (DC) loaded with the synthetic bcr-abl chimeric nonapeptide, GFKQSSKAL, led to a 150 times higher frequency of bcr-abl-specific CTL precursors in the spleen than in mice immunized with peptide alone. In vitro re-stimulation of DC-peptide-primed splenocytes resulted in substantial secretion of interferon gamma and augmented cytolytic activity against 12B1 targets. Finally, vaccination with peptide-loaded DC significantly prolonged survival of BALB/c mice that were challenged with 12B1 leukemia. The capacity to generate bcr-abl-specific CTL in vivo by DC-based immunization may have clinical implications in the treatment of CML.

Animals↗

Home intervention in the treatment of asthma among inner-city children.

BACKGROUND: In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty. OBJECTIVE: We sought to investigate allergen avoidance as a treatment for asthma among inner-city children. METHODS: One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels. RESULTS: There was a significant decrease in acute visits for asthma among children whose homes were visited (P < .001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P < .01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits. CONCLUSIONS: Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.

Adolescent↗

Biomarkers of immunotoxicity in fish: from the lab to the ocean.

Historically, host immunocompetence has been monitored using a battery of immune parameters. Recently, many of these same assays have been employed as biomarkers for predicting chemical-induced immunotoxicity in wildlife species. In this laboratory, assays measuring immunopathology, immune cell function, and host resistance against bacteria have been used successfully to assess immunotoxicity in laboratory-reared Japanese medaka (Oryzias latipes) and in feral fish populations. As an example of the latter, smallmouth bass collected from a PCB-contaminated site demonstrated significantly reduced phagocyte function and antioxidant activity compared to reference site fish. Taken together, these studies along with those from other investigators demonstrate the usefulness of immune assays as indicators to predict the toxicological risk associated with 'real-world' polluted aquatic environments.

Animals↗

Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines.

We have utilized a free-solution/isoelectric focusing technique (FS-IEF) to obtain fractions rich in multiple chaperone proteins from clarified A20 tumor lysates. Vaccines prepared from chaperone-rich fractions are capable of providing protective immunity in mice subsequently challenged intravenously with the same A20 B cell leukemia cells. This protection is at least equal to that provided by purified, tumor-derived heat-shock protein 70, which was the best chaperone immunogen in our hands against this aggressive murine leukemia model. Dosage escalation studies, however, revealed that increasing vaccine dosages actually abrogated the protective effects. The physical nature of the enriched chaperones indicates that they are associated in complexes, which may have implications for their function. FS-IEF is relatively simple, rapid, and efficient, thus making combined multi-chaperone therapy feasible.

Animals↗

Immunoprotective activities of multiple chaperone proteins isolated from murine B-cell leukemia/lymphoma.

Although the use of tumor-derived heat shock/chaperone proteins (HSPs) as anticancer vaccines is gaining wider study and acceptance, there have thus far been no reports concerning chaperone antitumor activities against disseminated hematological malignancies. We have devised an efficient and effective method for purification of the chaperone proteins grp94/gp96, HSP90, HSP70, and calreticulin from harvested A20 murine leukemia/lymphoma tumor material. We have demonstrated that these purified proteins, when used as vaccines, can induce potent and specific immunity against a lethal tumor challenge. Individual chaperone proteins were differentially effective in their abilities to provide immune protection. The increase in survival generated by the most effective chaperone vaccine, HSP70, resulted from at least a 2-log reduction in tumor burden. Syngeneic granulocyte macrophage colony-stimulating factor producing fibroblasts were injected at the site of vaccination in an attempt to augment the immune response. Surprisingly, localized granulocyte macrophage colony-stimulating factor production inhibited the protective effects of chaperone vaccination. These studies provide evidence that chaperone proteins can be isolated from B-cell tumors and used effectively to immunize against disseminated lymphoid malignancies.

3T3 Cells↗

Outbreak of sterile peritonitis among continuous cycling peritoneal dialysis patients.

BACKGROUND: Approximately 30,000 patients receive peritoneal dialysis in the United States. In August 1996, several dialysis centers from different states reported sterile peritonitis among CCPD patients using sterile peritoneal dialysis solution (PDS) from a single manufacturer. The manufacturer recalled 53 lots of PDS that had passed established industry guidelines and Food and Drug Administration (FDA) approved quality control tests [including endotoxin levels <0.5 endotoxin units (EU)/ml], but had pre-sterilization bacterial colony counts >1 cfu/ml. METHODS: At one outpatient dialysis center, Hospital of the University of Pennsylvania (HUP), we conducted a retrospective cohort study of all CCPD patients treated during July 15 to August 30, 1996. A case-patient was defined as any HUP patient with culture-negative peritoneal fluid with a white blood cell count >100/mm3, cloudy peritoneal fluid, and/or abdominal pain. PDS and tubing were cultured for bacteria and assayed for endotoxin. RESULTS: Overall, 14 of 28 patients had sterile peritonitis. The only risk factor identified was exposure to > or =1 lot of recalled PDS (14 of 22 vs. 0/6, P = 0.02); the more recalled lots received, the higher the attack rate (P = 0.0001). Five of 47 PDS bags had detectable endotoxin; recalled lots were more likely to have measurable endotoxin than nonrecalled lots (5/19 vs. 0/17, P = 0.05). When case-patients resumed CCPD using PDS from non-recalled lots, no further cases were reported. CONCLUSIONS: Our results suggest that this outbreak was caused by intrinsic PDS contamination with endotoxin. Pre-sterilization colony counts may be an important quality control indicator for CCPD fluids in conjunction with endotoxin levels.

Adult↗

Comparison of alcohol consumption patterns and social problems between women and men drink-drivers.

OBJECTIVE: To compare the sociodemographic characteristics, patterns of alcohol consumption and driving histories of women and men drink-drivers. DESIGN: Cross-sectional descriptive study. SETTING AND SUBJECTS: All 156 women who attended the Drink-Drive Program at St Vincent's Hospital, Melbourne, between January 1990 and December 1993, and an age-matched sample of 298 men attending in the same period. All had been disqualified from driving after a conviction for driving under the influence of alcohol. OUTCOME MEASURES: Self-reported weekly alcohol consumption and expenditure on alcohol at apprehension and during the program; blood alcohol level (BAL) at apprehension; demographic characteristics; number of previous drink-drive and other traffic convictions; and score on the Michigan Alcoholism Screening Test (MAST). RESULTS: Women had a higher educational level than men, and were more likely to be managers or professionals and to live in areas of high socioeconomic status. Women reported lower levels of weekly alcohol consumption at both apprehension (women: 15.2 standard drinks; men: 31.6 standard drinks) and during the program (women: 7.1 standard drinks; men: 12.0 standard drinks) but had similar BALs to men at apprehension (mean, 0.12% [26 mmol/L]). Sixty percent of women drank wine, or wine, beer and spirits, while 75% of men drank beer. Women had lower MAST scores than men (mean [standard deviation]: women, 5.8 [5.2]; men, 8.9 [8.2]). Women were less likely than men to have prior convictions for drink-driving or other traffic offences. CONCLUSION: Although women presented with similar blood alcohol levels to men, their drinking patterns and sociodemographic characteristics differ greatly. Health education for women drink-drivers needs to have a different strategy to that for men.

Alcohol Drinking↗

Platelet-derived growth factor indirectly stimulates angiogenesis in vitro.

We evaluated the effect of platelet-derived growth factor (PDGF) on capillary formation using an in vitro angiogenesis model system in which microvascular fragments and myofibroblasts (Mfs) isolated from rat epididymal lipid tissues were grown in co-culture. In this system Mfs induce capillary formation by producing an endothelial cell growth factor and by secreting extracellular matrix components that cause endothelial cells to form cordlike structures. Addition of PDGF enhances in vitro capillary growth. Although some recently described microvascular endothelial cells display PDGF receptors and respond to PDGF, we found no evidence for direct PDGF action on the rat epididymal microvascular endothelial cells. Rather, we found that PDGF increased the proliferation of Mfs, as well as the production of Mf-derived endothelial cell growth factor and matrix collagen type I. Our results suggest that even in cases where the microvasculature lacks PDGF receptors, PDGF may accelerate capillary formation by activating connective tissue cells in the vicinity of endothelial cells.

Animals↗

Does a blood alcohol level of 0.15 or more identify accurately problem drinkers in a drink-driver population?

OBJECTIVE: To determine whether a blood alcohol concentration (BAC) of 0.15 or more identifies accurately problem drinking in an apprehended drinking driver. DESIGN: Cross-sectional analytic study of 86 drink drivers ("diagnostic test study"). SETTING: St Vincent's Hospital, Melbourne, drink-driver education programme. SUBJECTS: Men aged between 18-25 years, applying for relicensing after disqualification, who were participants at 10 consecutive drink-driver education courses conducted in early 1987. OUTCOME MEASURES: Self-reports of the amount of alcohol consumed and the amount of money spent on alcohol per week, the standard Michigan Alcoholism Screening Test (MAST) score and the blood alcohol level at apprehension. The first three measures were used as reference standards for alcohol-related problems, against which the blood alcohol level was compared. MAJOR RESULTS: Scatter plots of BAC against amount consumed, amount spent and the MAST scores showed that a large proportion of the heaviest drinkers were not identified by the BAC. Log-transformed correlation coefficients were: for amount spent v. amount consumed, r = 0.73; for MAST score v. amount consumed, r = 0.52, and for MAST score v. amount spent r = 0.53. Correlating the BAC with the log of the MAST score gave r = 0.21, BAC with log of the amount consumed, r = 0.20, and BAC with log of the amount spent, r = 0.15. Comparing a BAC of 0.15 or more with a MAST score of greater than or equal to 5, we obtained a sensitivity of 0.36, a specificity of 0.76, a positive predictive value of 0.86, and a negative predictive value of 0.23. The prevalence of heavy drinking as measured by the MAST score was 0.80. CONCLUSION: A blood alcohol concentration of 0.15 or more identifies only a third of the problem drinkers in this sample of drink drivers. Although it selected a group of drinkers with alcohol-related problems, it missed most of the problem drinkers and did not reliably identify the heaviest drinkers.

Adult↗

Automated determination of human choriogonadotropin by use of microparticle capture analysis.

We evaluated a new microparticle enzyme immunoassay (MEIA) for human choriogonadotropin (hCG) in serum. This hCG assay is fully automated for the Abbott "IMx System," which has a dynamic range extending to 100,000 int. units/L. We tested 321 patients' sera, with hCG values ranging between 0 and 196,000 int. units/L by both the IMx hCG (y) and the Hybritech Tandem-E hCG (x) assays. Results correlated well (r = 0.972, slope = 0.87, y-intercept = 0.7). The IMx hCG assay is sensitive (0.21 int. units/L) and precise (CVs 2.4-8.7% for various hCG concentrations). No carryover to subsequent specimens was observed when specimens with values up to 10(6) int. units/L were tested, nor was any high-dose "hook" effect noted. The IMx hCG assay, which is specific for intact hCG molecules, is rapid (one to six samples in 17 min) and is a valid automated alternative to enzymatic and radioisotopic methodologies.

Autoanalysis↗

The Limulus amebocyte lysate assay. A rapid and sensitive method for diagnosing early gram-negative peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.

The Limulus amebocyte lysate (LAL) assay was used in a blinded, prospective fashion to analyze peritoneal fluids from 35 consecutive patients undergoing continuous ambulatory peritoneal dialysis (CAPD), who presented with clinical peritonitis. The results were correlated with standard microbiologic culture results. The LAL assay was positive in all three patients with gram-negative peritonitis, was appropriately negative in 24 of 28 gram-positive infections (sensitivity, 100%; specificity, 86%) and was positive in two of five cases in which there was no microbiologic growth. One of the two patients in this last group yielded a gram-negative organism two days later. It was then demonstrated that therapeutic concentrations of a variety of antibiotics (cefazolin sodium, gentamicin sulfate, tobramycin sulfate, ticarcillin disodium, penicillin G potassium, vancomycin hydrochloride, metronidazole hydrochloride, piperacillin sodium, and trimethoprim/sulfamethoxazole) did not interfere with the LAL assay. Together, these data indicate that the LAL assay is useful for identifying patients at high risk for gram-negative peritonitis and for excluding from possible aminoglycoside exposure the majority of patients with peritonitis undergoing CAPD, most of whom will have gram-positive infections. Furthermore, lack of antibiotic interference allows the possibility of monitoring treatment efficacy.

Anti-Bacterial Agents↗