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Biomedical subjects

D Berger

Publications and source records attributed to D Berger.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anti-endotoxin antibodies in human milk: correlation with infection of the newborn.

UNLABELLED: A longitudinal study was performed to investigate the content of human colostrum and milk of antibodies against endotoxins of Escherichia coli, Pseudomonas aeruginosa and Salmonella minnesota during the first 6 mo of lactation. The influence of the gestational age of the newborn and the prevalence of a systemic infection in the child on maternal antibody production were observed. Colostrum of mothers of term infants who had shown signs of systemic infection contained higher antibody concentrations compared to colostrum of mothers of healthy newborns. After the first week post partum, no difference in the milk's antibody content could be observed between these two groups. Antibody titres rose from 2 wk to 6 mo post partum (p < 0.001). Milk of mothers of preterm infants with signs of systemic infection contained higher antibody titres than milk of mothers of preterm infants without infection throughout the observation period. This difference reached statistical significance 3 wk after delivery (p < 0.05). The corrected endotoxin antibody levels against all tested antigens in milk of mothers of preterm infants with infection 6 mo post partum were 6+/-3.5 times as high as 2 wk post partum. CONCLUSIONS: Breast milk contains anti-endotoxin antibodies. The particularly high levels of antiendotoxin antibodies in cases of neonatal infection may present a special maternal protection for premature infants.

Antibodies↗
PubMed2000

Association of endotoxemia and production of antibodies against endotoxins after multiple injuries.

BACKGROUND: Endotoxemia after injury has been a controversial issue. Endotoxins stimulate the innate and adaptive immune system. OBJECTIVE: To investigate endotoxemia and its effects on the production of antiendotoxin antibodies of cultured mononuclear cells of patients with multiple injuries. METHODS: Blood samples of 20 patients with multiple injuries were collected up to 12 days after trauma. The endotoxin concentration was measured in the plasma, and mononuclear cells were isolated and cultured. Specific antibodies against two lipopolysaccharides, one lipid A preparation, and alpha-hemolysin of Staphylococcus aureus were measured in the cell culture supernatant by an enzyme-linked immunosorbent assay. RESULTS: Endotoxemia peaked at admission of the patients, decreasing thereafter to almost normal values within 5 days. Isolated mononuclear cells synthesized antibodies against all tested antigens with a peak at or between day 5 and day 7. The increase was significant for immunoglobulin (Ig)A and IgM specific to all endotoxins tested and for IgA specific to alpha-hemolysin. However, there were no significant changes of the concentrations of total IgM, IgA, and IgG. All specific IgG remained unaffected. CONCLUSION: Patients with multiple injuries initially have temporary endotoxemia. Endotoxin may be suggested as a stimulator of the synthesis of antiendotoxin antibodies, in particular of the IgA and IgM class in patients with multiple injuries.

Adult↗
PubMed2000

Endotoxemia and mediator release during cardiac surgery.

Endotoxemia in man is a controversial issue. However, endotoxin is a potent trigger of the inflammatory response. Therefore, endotoxin translocation and mediator release was investigated in patients undergoing cardiac surgery. In 40 patients (13 women and 27 men, ages ranging from 30 to 73 years with a median of 60 years), plasma concentrations of endotoxin, interleukin-6 (IL-6), and C-reactive protein (CRP) were determined during and after cardiovascular bypass. In a subgroup of 10 patients, myeloid-related proteins: MRP8, MRP14, and the soluble heterocomplex (MRP8/MRP14) levels were additionally studied. A significant increase (p < 0.01) of plasma endotoxin concentrations was found during surgery, culminating in a peak (median value of 0.82 EU/mL) during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the 5th postoperative day, whereas those of interleukin-6 rose at the end of the operation and were at their highest level 6 hours postoperatively (median value of 218 pg/mL). CRP levels were increased 24 hours postoperatively with a median value of 114 mg/L and peaked on day 2 (191 mg/L). A statistically significant correlation between the intraoperative endotoxin plasma concentrations and IL-6 concentrations was established (p < 0.05). The MRP8/MRP14 heterocomplex increased until day 2 after surgery, except MRP14, which showed the highest level at day 1 (55 ng/mL). Cardiac surgery is associated with endotoxemia and a marked acute-phase response. Therefore, endotoxin must be regarded as a pathophysiologic mediator. The role of the gut as a source of endotoxemia following cardiac surgery deserves further attention.

Acute-Phase Reaction↗
PubMed2000

How to identify global markets that are ready for managed care.

As international risk carriers observe increasing medical loss ratios, many have flocked to managed care in an attempt to control medical costs while allowing for the measurement of care leading to improved quality. These same risk carriers often find it difficult to determine which managed care programs will produce the desired effects. However, it is not always clear why American health care concepts do not always produce the desired results in some international markets.

Cost Control↗
PubMed1999

Novel multidrug resistance reversal agents.

A series of 59 alpha-aryl-alpha-thioether-alkyl, -alkanenitrile, and -alkanecarboxylic acid methyl ester tetrahydroisoquinoline and isoindoline derivatives (15a-48) were synthesized and evaluated as multidrug resistance (MDR) reversal agents. The compounds were tested on S1-B1-20 human colon carcinoma cells selected for resistance to bisantrene. Both the cytotoxicity of the reversal agents and their ability to resensitize the cells to bisantrene were determined. All but two of these compounds (15q, 40) were more effective MDR reversal agents in vitro than verapamil (VRP), a calcium channel antagonist which also has been shown to possess MDR modulating activity. Several showed good activity in this assay (IC50's < 0.5 microM), the most potent being isoindolines 44 (IC50 0.26 microM) and 46 (IC50 0.26 microM) and tetrahydroisoquinolines 47 (IC50 0.29 microM) and 15m (IC50 0.30 microM). A number of compounds were evaluated in vivo against vincristine (VCR)-resistant murine P388 leukemia, as well as against human epidermoid carcinoma KB/8.5 implanted sc in athymic mice. The reversal agents which consistently showed the highest activity, together with low toxicity, were alpha-aryl-alpha-thiotolylalkanenitrile tetrahydroisoquinoline derivatives with electron-rich alkoxy substituents on the aromatic rings. Of the tested compounds, the most effective reversal agents for both tumor lines were 15h (33% increased life span at 12.5 mg/kg, 0.2 mg/kg VCR versus VCR alone in the VCR-resistant P388 leukemia model and 59% relative tumor growth at 50 mg/kg, 8 mg/kg doxorubicin versus doxorubicin alone in the KB/8.5 model) and 39a (48% increased life span at 50 mg/kg, 0.2 mg/kg VCR versus VCR alone in the VCR-resistant P388 leukemia model and 46% relative tumor growth at 25 mg/kg, 8 mg/kg doxorubicin versus doxorubicin alone in the KB/8.5 model). The mechanism of action of these compounds is believed to involve blocking the drug efflux pump, P-glycoprotein.

Animals↗
PubMed1999

Elevated levels and functional capacity of soluble CD40 ligand in systemic lupus erythematosus sera.

OBJECTIVE: To measure soluble CD40 ligand (sCD40L) in sera from patients with systemic lupus erythematosus (SLE) and to study the functional capacity of sCD40L in mediating B cell activation. METHODS: A 2-site enzyme-linked immunosorbent assay (ELISA) was used to measure sCD40L in the sera of 66 SLE patients, 30 disease control patients, and 23 healthy subjects. Induction of B cell activation antigen expression was used to assess the functional capacity of sCD40L in SLE sera. RESULTS: The mean concentration of sCD40L was statistically significantly higher (P < 0.0001) in SLE patients than in disease controls or healthy subjects, and segregation of SLE patients by severe, moderate, or mild extent of disease showed a relationship between disease severity and sCD40L concentration. Western blot analysis demonstrated the presence of the 18-kd band of sCD40L in SLE sera, and the results of a 1-site ELISA protocol suggested that some of the product in SLE sera was present in dimer or trimer form. Functional studies showed that 10 ng/ml of recombinant CD40L, a level present in some SLE sera, induced increased expression of CD95 on B cells. Several SLE sera also induced CD95 or CD86 on Ramos B cells, a result that was inhibited by anti-CD40L monoclonal antibodies. CONCLUSION: The soluble form of CD40L is present in the sera of most patients with SLE and may have the capacity to mediate B cell activation. Aberrant expression of CD40L might be predicted to result in activation of bystander B cells, including those that have encountered self antigens, and to contribute to autoantibody secretion.

Antigens, Surface↗
PubMed1999

Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis.

BACKGROUND: Impaired renal function in patients with liver cirrhosis is a serious complication and is characterized by sodium and water retention in the absence of identifiable specific causes of renal dysfunction. The endothelin system has been shown to be activated in liver cirrhosis and might contribute to impaired renal function. However, the mechanisms leading to an activation of the endothelin system in these patients and the effects of an activated endothelin system on renal function in these patients are as yet unknown. METHODS: To determine the correlation between the activity of the endothelin system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-1 concentrations by reversed phase-HPLC followed by an endothelin RIA and performed an oral water load tests in 10 healthy control subjects and 43 patients with liver cirrhosis. In addition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrhosis. RESULTS: This study showed that the endothelin system is activated in patients with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentration compared to healthy controls, whereas plasma ET-1 is only increased 2.74-fold in Child A patients. An oral water load test revealed a highly significant (P < 0.0001) inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water load. Plasma endotoxin, a well-known stimulus of ET-1, is significantly (P < 0.03) correlated with plasma ET-1 in cirrhotic patients. The ET-1 concentrations in the ascites of patients with liver cirrhosis were lower and not related to plasma ET-1. CONCLUSION: The activity of the endothelin system in patients with liver cirrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We observed a highly significant inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water and sodium load, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.

Case-Control Studies↗
PubMed1999

Changes in endotoxin-binding proteins during major elective surgery: important role for soluble CD14 in regulation of biological activity of systemic endotoxin.

Assessment of circulating endotoxin during the perioperative period, which is only demonstrated by the Limulus amebocyte lysate (LAL) test, may be modulated by several endotoxin-binding proteins. Endotoxin-neutralizing capacity (ENC) and the plasma levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein, and bactericidal/permeability-increasing protein (BPI) were determined in 40 patients 6 h prior to skin incision for major abdominal surgery. The bioactivity of plasma endotoxin was tested by the polymyxin B-inhibited stimulatory activity of the plasma samples on healthy monocytes as measured by the release of tumor necrosis factor alpha. Plasma endotoxin levels in almost all patients increased from 0.05 +/- 0.01 to 0.23 +/- 0.03 experimental units (EU) per ml (P < 0.001); more specifically, 17 of 40 samples showed endotoxin levels of greater than 0.2 EU per ml and corresponding reductions in ENC. Soluble CD14 plasma levels were decreased from 5. 6 +/- 0.3 to 4.6 +/- 0.3 microg per ml (P < 0.05). ENC was strongly correlated with the sCD14 plasma concentration throughout the period of observation. The addition of sCD14-neutralizing monoclonal anti-sCD14 antibodies reduced ENC both pre- and postoperatively. No correlation could be established between ENC and the plasma levels of BPI, high-density lipoproteins, or low-density lipoproteins determined by measuring the concentrations of apoprotein A and apoprotein B. Biologically active endotoxin was found in only 6 of 17 samples with endotoxin levels greater than 0.2 EU per ml in the LAL test. These samples could be characterized by their perioperative loss of at least 35% of their sCD14. No change in sCD14 was detected in the remaining 11 samples. The perioperative loss of ENC is partly caused by the loss of sCD14 resulting from its consumption by endotoxin reaching the bloodstream. This study demonstrated the role of sCD14 on the bioactivity of circulating endotoxin in a human model of endotoxemia after major abdominal surgery.

Abdomen↗
PubMed1999

Endotoxin release due to ciprofloxacin measured by three different methods.

Antibiotics are known to induce the release of bioactive endotoxin (LPS) from gram-negative bacterial cells. Because varying data have been published on the influence of quinolone antibiotics on LPS liberation, we studied the effect of ciprofloxacin on a culture of Escherichia coli by determining bacterial killing and free LPS concentrations in comparison with imipenem and ceftazidime. LPS levels were measured by three different methods, namely (1) the Limulus amebocyte lysate test, (2) an ELISA method based on capture of LPS by monoclonal antibodies, and (3) indirect determination by measuring the ability of antibiotic-induced LPS to trigger TNFalpha release from a monocytic cell line. With both the Limulus and ELISA tests, a low endotoxin-releasing activity of ciprofloxacin was confirmed. In contrast to previous studies, this LPS also had low bioactivity in terms of TNFalpha induction. Limulus LPS determinations correlated more precisely with LPS bioactivity than did ELISA values, an observation which underlines the crucial role of LPS determination methods in studies of antibiotic-induced LPS release.

Anti-Infective Agents↗
PubMed1999

No evidence for association between IDDMK(1,2)22, a novel isolated retrovirus, and IDDM.

In the past, endogenous retroviral sequences have been isolated from patients suffering from different kinds of autoimmune diseases. Recently, a full length retroviral genome, termed IDDMK(1,2)22, was isolated from patients with new-onset IDDM. This genome contains a major histocompatibility complex II-dependent superantigen within its envelope gene. The viral sequence was found in ten patients with new-onset IDDM, but not in age-matched control subjects (Conrad et al. [9]). We searched for the presence of this viral genome by nested reverse transcription-polymerase chain reaction (RT-PCR) in a cohort of six patients with new-onset IDDM and six control subjects of the same age. We found all samples to be positive without any differences between patients and control subjects. The same results were obtained with supernatants of activated peripheral blood mononuclear cells. We performed isopycnic ultracentrifugation in sucrose density gradients on all samples and were unable to detect particles of the new virus in any of our samples. However, positive signals were obtained from all pellet fractions. RNase, DNase treatment and nested PCRs without reverse transcription showed that the positive signals were probably derived from intracellular RNA and DNA. In summary, no correlation between a positive nested PCR signal for IDDMK(1,2)22 and diabetes was found indicating that the new sequence represents just an additional member of the human endogenous retrovirus (HERV) family with lack of an exogenous counterpart.

Adult↗
PubMed1999

Alexithymic traits as predictors of difficulties with adjustment in an outpatient cohort of expatriates in Tokyo.

The purpose of this study was to examine whether alexithymic characteristics, which are thought to be related to poor coping with stress, would be associated with variables thought to reflect adjustment to life abroad. The subjects were 56 expatriates living in Tokyo, Japan. The Expatriate Adaptation Inventory, the Toronto Alexithymia Scale, and the Social Support Questionnaire of the Stress and Coping Inventory were given to the subjects. Scores on alexithymia were significantly associated with dissatisfaction with life abroad, higher satisfaction with life in one's home country prior to departure, and higher ratings on the perception of poor social support. An alexithymia variable, difficulty identifying feelings, was a significant predictor of dissatisfaction with life abroad and satisfaction with life in the home country. The results suggest that, because alexithymia was associated with lower satisfaction with life abroad and higher satisfaction in the home country prior to departure, it may be a predictor of adjustment difficulties when individuals live abroad. Empirical confirmation is needed.

Adaptation, Psychological↗
PubMed1999

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗
PubMed1999

A brief history of medical diagnosis and the birth of the clinical laboratory. Part 1--Ancient times through the 19th century.

From tasting urine to microscopy to molecular testing, the sophistication of diagnostic techniques has come a long way and continues to develop at break-neck speed. The history of the laboratory is the story of medicine's evolution from empirical to experimental techniques and proves that the clinical lab is the true source of medical authority. Part 1 in a 2-part series.

Chronology as Topic↗