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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

At least 235 records · Page 13Linked to original sources

The function of the soluble IL-6 receptor in vivo.

Interleukin-6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B-cells, T-cells, keratinocytes, neuronal cells, osteoclasts and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal-transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as AIDS, rheumatoid arthritis and others. The function of the soluble IL-6R in vivo is unknown. To discriminate between the biologic function of hIL-6 alone and that of the hIL-6/hsIL-6R complex, mice transgenic for human IL-6, for the human soluble IL-6R and for both, human IL-6 and the human soluble IL-6R were analyzed and compared with nontransgenic littermates. While IL-6 transgenic mice exhibit elevated acute phase protein levels and develop plasmacytomas, hsIL-6R single transgenic mice are hypersensitized towards human IL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the acute phase response persists for a longer period of time and the IL-6 plasma half life was markedly prolonged. IL-6/sI1-6R mice, however, develop massive hepatosplenomegaly caused by extramedullary hematopoisis in these organs. In IL-6- and IL-6R-single transgenic mice, no such effects were observed. Our study discloses a novel biologic effect of the hIL-6/hsIL-6R complex, which is clearly distinct from that of hIL-6 alone. We provide evidence that the activation of the gp130 signal transducer represents a major stimulation of growth and differentiation of hematopoietic progenitor cells.

Acute-Phase Proteins↗

Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women.

Risk factors for cervicovaginal human papillomavirus (HPV) infection were investigated in 604 college women. HPV was detected in 168 (27.8%) of the subjects by L1 consensus primer polymerase chain reaction, Southern blot hybridization, or both. Significant independent risk factors for HPV (P < .05) included age (odds ratios [ORs]: 2.6 for 21-23 years old and 1.6 for > 23, vs. < or = 20), ethnicity (ORs: 3.2 for black, 2.2 for Hispanic, vs. white/other), number of lifetime male vaginal sex partners (ORs: 4.5 for 2, 5.8 for 3 or 4, 10.3 for > or = 5, vs. 1), living with smokers (OR: 1.9), male partner's number of lifetime sex partners (ORs: 2.1 for 2 or 3, 3.1 for 4-10, 2.7 for > or = 11, vs. 1), duration of sexual relationship for > 12 months (OR: 0.6), and male partner currently in college (OR: 0.6). These data demonstrate that the predominant risk factors for genital HPV infection in young women are related not only to their own sexual behaviors but also to those of their male partners.

Adult↗

Treatment of obstructive sleep apnea with a self-titrating continuous positive airway pressure (CPAP) system.

Conventional manually adjusted continuous positive airway pressure (CPAP) is an effective therapy for sleep-disordered breathing. We prospectively investigated the efficacy of a self-titrating nasal CPAP system in the acute treatment of obstructive sleep apnea (OSA) syndrome. Twenty patients with moderately severe OSA [apnea hypopnea index (AHI) > 15/hour] were enrolled in a randomized, controlled, prospective clinical trial. An initial diagnostic sleep study was performed, followed by randomization to a manually adjusted CPAP titration on one night and self titrating CPAP on the other night. On the conventional CPAP night, the CPAP was manually adjusted until abolition of all apneas and electroencephalographic (EEG) arousals, whereas the self-titrating CPAP was set in automatic mode at lights out. The self-titrating CPAP system utilized an algorithm based on airway vibration patterns to detect airway stability. The AHI decreased from 50.8 +/- 28.8/hour [mean +/- standard deviation (SD)] at baseline to 3.8 +/- 3.1/hour (p < 0.005) during manually adjusted and 6.1 +/- 5.3/hour (p < 0.005) during self-titrating CPAP. The arousal index (Ar-I) decreased from 34.1 +/- 23.1/hour (baseline) to 11.2 +/- 5.0/hour on manual adjustment (p < 0.005) and 11.3 +/- 0.3/hour on self titration (p < 0.005), whereas total sleep time was unchanged. No significant differences in any measure of oxygenation or sleep architecture were observed between the manually adjusted and self-titrating CPAP nights except that the lowest arterial oxygen saturation (SaO2) was higher with manual titration (84.4 +/- 4.2% vs. 79.9 +/- 9.7%, p < 0.05). The maximum pressure required for abolition of apneas and arousals was significantly lower (p < 0.05) during the self-titrating study (10.1 +/- 3.8 cmH2O) as compared to manually adjusted CPAP (12.3 +/- 3.9 cmH2O). Failure to increase pressure and failure to maintain minimum pressure occurred in 7 of the 20 subjects during the self-titrating study. This required manual resetting of the system in five subjects, but the system self-corrected in two subjects. An unsupervised study would have resulted in undertreatment of OSA. Based on a single-night laboratory study, self-titrating CPAP was well tolerated and improved OSA and sleep architecture comparable to manually adjusted CPAP. The future modifications of this prototype will require further research to assess its efficacy and safety in the laboratory and home environments before its recommendation for general long-term use.

Adult↗

Fetal and neonatal development of antithrombin III plasma activity and liver messenger RNA levels in sheep.

In healthy term human newborns a unique hemostatic balance exists with reduced plasma concentrations of several coagulant and anticoagulant proteins, including antithrombin III (AT III). In preterm newborns even lower AT III concentrations are observed, with an associated thromboembolic risk. As part of our study program on the gene regulation of AT III, we investigated whether the increase in plasma AT III activity during fetal and neonatal development is particularly controlled at the transcriptional level. Plasma AT III activity and liver AT III mRNA content between the 8th wk of gestation and the 4th wk after birth were determined in sheep. AT III activity gradually increased from 34% of the mean adult level at 8-10 wk of gestation to 86% (2.5-fold) at term (21 wk), and remained in the adult range after birth. The mean body weight, and thus plasma volume, increased 57-fold. Therefore, the total plasma AT III activity increased 140-fold. The total liver AT III mRNA content increased only 14-fold between these fetal stages, mainly due to increased liver weight. Therefore, the total plasma AT III activity increased 10-fold more than the liver AT III mRNA content. In the neonatal period between d 1-3 and 28, the total plasma AT III activity increased only 2-fold more than the liver AT III mRNA content. We conclude that the increase in plasma AT III activity during the fetal period, and similarly the neonatal period, is not regulated at the transcriptional level. Furthermore, a unique fetal isoform of AT III was detected in sheep. This isoform had a 2500-D higher molecular mass compared with the other fetal, neonatal, and adult AT III isoform, and disappeared from the circulation between d 2 and 7 after birth. These AT III isoforms differ in their carbohydrate moiety.

Animals↗

Functional endoscopic sinus surgery under local anaesthesia: possibilities and limitations.

Functional endoscopic sinus surgery under local anaesthesia with one single intramuscular injection of systemic premedication (pethidine and promethazine) and careful local preparation (decongestive nose drops, cocaïne application and lidocaine infiltration). It is well tolerated and accepted in 95% of the patients. Blood loss is minimal and pain during the operation is rare. Major and minor orbital and intracranial complications were not seen. Local anaesthesia with this kind of surgery offers many advantages and is preferable to general anaesthesia when possible.

Adjuvants, Anesthesia↗

[Listeriosis in a rabbitry].

An enzootic of listeriosis in a rabbitry is reported. Listeria monocytogenes serotype 1/2a was isolated from the organs of a doe, which had died of septic metritits. From aborted fetuses of two other does Listeria monocytogenes serotype 1/2b and 4b were cultured, respectively. In feed samples of the rabbitry Listeria monocytogenes strains of the serotypes 1/2b and 4b besides the apathogenic Listeria species Listeria seeligeri and Listeria innocua were detected. Serological studies with agglutination test and complement fixation test on double serum samples of does, which had aborted, pointed to listeric infections as the cause of abortion. A doe, which had aborted and failed to become pregnant again, showed serosal adhesions of both uterine tubes and a sterile pyometra. Therefore, previous infection of the uterus by Listeria monocytogenes should be considered as a cause of infertility.

Abortion, Veterinary↗

A new hepatocyte stimulating factor: cardiotrophin-1 (CT-1).

Recently, a novel cytokine, cardiotrophin-1 (CT-1), was cloned and found to induce cardiac myocyte hypertrophy in vitro. Amino acid sequence similarity showed CT-1 to be a member of the IL-6/LIF/CNTF/OSM/IL-11 cytokine family. Since all known members of the IL-6 cytokine family induce an hepatic acute phase protein (APP) gene expression, we investigated the ability of CT-1 to induce a liver acute phase response. Upon stimulation of rat hepatoma cells, CT-1 and LIF induced the strongest rat fibrinogen mRNA expression, OSM and IL-6 induced a less pronounced response. When human hepatoma cells and primary rat hepatocytes were stimulated with CT-1, the expression of human haptoglobin and rat alpha 2-macroglobulin mRNA was induced. The induction of the acute phase response was dose- and time-dependent. In this study we demonstrate that CT-1, a novel cytokine belonging to the IL-6 cytokine family, is a hepatocyte stimulating factor.

Acute-Phase Proteins↗

A redrawn Vandenberg and Kuse mental rotations test: different versions and factors that affect performance.

The available versions of the Vandenberg and Kuse (1978) Mental Rotations Test (MRT) have physically deteriorated because only copies of copies are available. We report results from a redrawn version of the MRT and for alternate versions of the test. Males perform better than females, and students drawn from the physical sciences perform better than students drawn from the social sciences and humanities, confirming other reports with the original version of the MRT. Subjects find it very hard to perform the MRT when stimuli require rotation along both the top/bottom axis and the left/right axis. The magnitude of effect sizes for sex (which account, on average, for some 20% of the variance) does not increase with increasing difficulty of the task. Minimal strategy effects were observed and females did not perform differently during the menstrual period as opposed to the days between the menstrual periods. Practice effects are dramatic, confirming other reports with the original MRT, and can also be shown to be powerful in a transfer for practice paradigm, where test and retest involve different versions of the MRT. Main effects of handedness on MRT performance were not found.

Adult↗

Posttransfusional, LKM-1-autoantibody-positive hepatitis C virus infection, cryoglobulinemia, and aplastic anemia.

Aplastic anemia is occasionally caused by viral hepatitis, hepatitis C virus being the most important factor. Pathogenetically, decreased bone marrow function, abnormalities of the bone marrow microenvironment, and immune-mediated suppression of hematopoiesis are important. Hepatitis C virus infection is associated with a variety of extrahepatic manifestations including autoimmune features like cryoglobulinemia, Sjögren's syndrome, and autoimmune hepatitis. Here we report the case of a 42-year-old man with aplastic anemia due to posttransfusional hepatitis C virus infection associated with cryoglobulinemia and LKM-1 autoantibodies. Following a triple immunosuppressive therapy, there was a complete reconstitution of the bone marrow. Serum HCV-RNA as well as plus- and minus-stranded HCV-RNA in peripheral blood mononuclear cells (PBMC) were detected before immunosuppressive therapy. After therapy, serum HCV-RNA persisted. Furthermore, PBMC now were positive for plus-stranded RNA only. However, in bone marrow-derived precursor cells we failed to demonstrate HCV molecules after therapy. This would argue for reconstituted PBMC from newly generated uninfected precursor cells. It remains unclear as to whether the autoimmune character of the disease or the hepatitis C virus infection itself have contributed to the pathogenesis of the aplastic anemia.

Adult↗

Chronic low back pain and inaccurate predictions of pain: is being too tough a risk factor for the development and maintenance of chronic pain?

The present study tests whether chronic low back pain (CLBP) patients show a tendency to overpredict or to underpredict pain. Twenty CLBP patients and 20 healthy controls underwent 6 trials of laboratory induced pressure pain. Ratings of predicted and experienced pain intensity were obtained. In contradiction with the hypothesis that CLBP patients show a generalized tendency to overpredict pain, CLBP patients showed a tendency to underpredict the laboratory pain, whereas controls appeared to be more accurate. This finding replicates a previous finding, that there may be a substantial group of CLBP patients who underestimate pain. The tendency to underpredict pain may constitute a risk factor for the development and maintenance of CLBP.

Adaptation, Psychological↗

Utilization of laboratory resources: developments in knowledge-based ordering systems.

This paper describes two rule based decision support systems. The first system is used to screen incoming test requests for adequacy on the basis of signs and symptoms volunteered by the requesting GPs. The system was tested using a database of 794 requests for a TSH test. About 17% of the test requests were correctly identified as unnecessary. In total, 0.5% of the tests were incorrectly labelled as unnecessary. This concerned 4% of the patients that appeared to have hyperthyroidism and 23% of the patients that appeared to have hypothyroidism on the basis of TSH and FT4 results. The other system is a rule-based clinical decision support system for the requesting of laboratory investigations, originally designed for use at a hospital within the UK, that was implemented in a predominantly French-speaking hospital in Belgium. This involved the modification of the system to allow multilingual operation, and also the implementation of a completely new set of investigation protocols. The purpose of this study was to assess the transferability, both of the system itself, and of its benefits. The system was introduced gradually and has only recently been in full operation. However, the findings from the first months of routine use of the system indicate that the transfer of the system to a different clinical environment has been successful. Although it is too early to assess fully the impact on laboratory utilization, the clinicians believe that it is improving the appropriateness of investigations.

Artificial Intelligence↗

Renal response to candoxatrilat in patients with heart failure.

OBJECTIVES: Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied. BACKGROUND: Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study. METHODS: In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing. RESULTS: All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS: Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

Aged↗

Isolation of atypical mycobacteria from tap water in hospitals and homes: is this a possible source of disseminated MAC infection in AIDS patients?

Infections caused by mycobacteria other than tuberculosis (MOTT), especially Mycobacterium avium complex (MAC), are common in AIDS patients, but rare in immunocompetent persons. The route of transmission is unknown, but tap water could provide a possible source of infection: MAC was isolated from tap water in the U.S.A. but this has not been reported in Germany. We therefore investigated tap water in Berlin for the presence of mycobacteria and compared radiometric (Bactec) and standard plate culture methods processing large volumes of water samples. The Bactec method yielded equal results compared to standard methods but had the advantage of easy handling. Mycobacteria were isolated from 50/118 (42.4%) samples and from 21/30 (70%) sites. The most frequently isolated species was Mycobacterium gordonae (from 28% samples and from 53.3% sites); MAC was isolated from two samples only (1.7%).

AIDS-Related Opportunistic Infections↗