Biomedical subjects

M Schafer

Publications and source records attributed to M Schafer.

At least 19 recordsLinked to original sources

PubMed2003

Painful inflammation-induced increase in mu-opioid receptor binding and G-protein coupling in primary afferent neurons.

Opioids mediate their analgesic effects by activating mu-opioid receptors (MOR) not only within the central nervous system but also on peripheral sensory neurons. The peripheral analgesic effects of opioids are best described under inflammatory conditions (e.g., arthritis). The present study investigated the effects of inflammation on MOR binding and G-protein coupling of full versus partial MOR agonists in dorsal root ganglia (DRG) of primary afferent neurons. Our results show that Freund's complete adjuvant (FCA) unilateral hindpaw inflammation induces a significant up-regulation of MOR binding sites (25 to 47 fmol/mg of protein) on DRG membranes without affecting the affinity of either full or partial MOR agonists. In our immunohistochemical studies, the number of MOR-immunoreactive neurons consistently increased. This increase was mostly caused by small-diameter nociceptive DRG neurons. The full agonist DAMGO induced MOR G-protein coupling in DRG of animals without FCA inflammation (EC50 = 56 nM; relative Emax = 100%). FCA inflammation resulted in significant increases in DAMGO-induced MOR G-protein coupling (EC50 = 29 nM; relative Emax = 145%). The partial agonist buprenorphine hydrochloride (BUP) showed no detectable G-protein coupling in DRG of animals without FCA inflammation; however, partial agonist activity of BUP-induced MOR G-protein coupling was detectable in animals with FCA inflammation (EC50 = 1.6 nM; relative Emax = 82%). In behavioral studies, administration of BUP produced significant antinociception only in inflamed but not in noninflamed paws. These findings show that inflammation causes changes in MOR binding and G-protein coupling in primary afferent neurons. They further underscore the important differences in clinical studies testing peripherally active opioids in inflammatory painful conditions.

Animals↗

PubMed2002

Intrapericardial urokinase irrigation and systemic corticosteroids: an alternative to pericardectomy for persistent fibrino-purulent pericarditis.

A 39-year-old man was admitted for upper abdominal pain and shortness of breath. The chest roentgenogram demonstrated cardiomegaly and left lower lobe atelectasis. Echocardiography showed circumferential pericardial effusion with signs of cardiac tamponade. Pericardial biopsy and fluid analysis were consistent with fibrino-purulent pericarditis. Despite broad-spectrum antibiotics, percutaneous and subsequently surgical drainage, pericardial effusion and tamponade recurred. We report successful treatment of a non-resolving fibrino-purulent pericardial effusion by combined intrapericardial irrigation of fibrinolytics and systemic corticosteroids administration as an alternative to pericardectomy.

Acute Disease↗

PubMed2001

Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review.

BACKGROUND: The usefulness of intravenous patient-controlled analgesia (PCA) with opioids for postoperative analgesia is not well defined. METHODS: We systematically searched (MEDLINE, EMBASE, Cochrane Library, bibliographies, any language, to January 2000) for randomised trials comparing opioid-based PCA with the same opioid given intramuscularly, intravenously, or subcutaneously. Weighted mean differences (WMD) for continuous data, relative risks (RR) and numbers-needed-to-treat (NNT) for dichotomous data were calculated with 95% confidence intervals (CI) using fixed and random effects models. RESULTS: Data from 32 trials were analysed: 22 (1139 patients) were with morphine, five (682) with pethidine, three (184) with piritramide, one (47) with nalbuphine and one (20) with tramadol. In three morphine and one pethidine trial (352 patients), more patients preferred PCA (89.7% vs. 65.8%, RR 1.41 (95%CI 1.11 to 1.80), NNT 4.2). Combined dichotomous data on pain intensity and relief, and the need for rescue analgesics from eight morphine, one pethidine, one piritramide, and one nalbuphine trial (691 patients), were in favour of PCA (RR 1.22 (1.00 to 1.50), NNT 8). In two morphine trials (152), pulmonary complications were more frequently prevented with PCA (100% vs. 93.3%, RR 1.07 (1.01 to 1.14), NNT 15). There was equivalence for cumulative opioid consumption, pain scores, duration of hospital stay, and opioid-related adverse effects. CONCLUSION: These trials provide some evidence that in the postoperative pain setting, PCA with opioids, compared with conventional opioid treatment, improve analgesia and decrease the risk of pulmonary complications, and that patients prefer them.

Acute Disease↗

PubMed1996

Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia.

Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown. This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1beta (IL-1). A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose-dependently attenuated by intraplantar but not by intravenous alpha-helical CRF. IL-1 receptor antagonist is ineffective. Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect. Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia. Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity. These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue. Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS.

Analgesics, Opioid↗

PubMed1996

Latex allergy and anaphylaxis in a child undergoing craniofacial surgery.

This case report represents an example of latex anaphylaxis in a child with a history of multiple previous surgeries without any complications. Obviously, the patient had not shown evidence of being sensitized until this particular surgery, where she had multiple sources of latex exposure, e.g., Foley catheter, blood pressure cuff, rubber gloves, and clear adhesive tape. If a more careful history had been taken, the diagnosis of latex allergy might have been suspected, for upon further questioning after surgery, the mother reported multiple incidences of urticarial reactions to rubber gloves and clothes with elastic waist bands. In summary, this case report highlights the importance of a careful history and the need for a high index of suspicion of potential latex allergy in children who acquire sensitization to latex because they require multiple surgical procedures for anatomic correction of congenital abnormalities. One week after this episode, the patient returned to the operating room for completion of her surgery. All latex was avoided, and there were no complications.

Anaphylaxis↗

PubMed1996

Palliation of carcinoma of the oesophagus with brachytherapy and the Didcott dilator.

Forty-one patients with oesophageal cancer who developed strictures after high dose rate intraluminal brachytherapy were dilated using a slow continuous dilator (Didcott dilator). After dilatation, all patients were evaluated monthly for relief of dysphagia. At the end of the 1st month, 41 patients were evaluable: 28 had no dysphagia while 13 had improvement; at the end of the 2nd month, 40 were evaluable, 26 had no dysphagia while 14 had improvement; at the end of the 3rd month, 34 patients were evaluable, 24 had no dysphagia while 10 had improved. Three patients developed worsening of dysphagia owing to tumour recurrence among 32 patients who were evaluable at the end of the 4th month. Five patients developed worsening of dysphagia among the 26 patients who were evaluable at the 5th month due to tumour. These patients were dilated with the Didcott dilator and were treated with further brachytherapy. At the end of the 6th month, 14 patients were evaluable; seven had no dysphagia, while seven had improvement over their presenting dysphagia scores. Slow continuous dilatation using the Didcott dilator is very effective in the dilatation of strictures after high dose rate intraluminal brachytherapy. Dilatation is prolonged and sustained and a single dilatation is usually enough to maintain patency.

Adult↗

PubMed1995

Integrated image processing in clinical applications: the HELIOS approach.

This paper describes the approach of the European HELIOS project to integrate image processing tools into ward information systems. The image processing tools are the result of the basic research in image analysis in the Department Medical and Biological Informatics at the German Cancer Research Center. Tools for the analysis of 2-dimensional images and 3-dimensional data volumes with 3-dimensional reconstruction and visualization are part of the Image Related Services of HELIOS.

Europe↗

PubMed1994

Heavy ion induced DNA double strand breaks in cells of E. coli.

Vegetative cells of E. coli differing in their radiosensitivity have been used in heavy ion irradiation experiment. Besides inactivation measurements also the induction of DNA double strand breaks (DSB) have been measured using the method of pulse-field gel electrophoresis. This method allows to separate linear DNA with length up to 8 Mio base pairs. After irradiation with heavy ions we find a higher amount of low molecular weight fragments when compared to sparsely ionizing radiation. This agrees with the idea that heavy ions as a structured radiation have a high probability to induce more than one strand break in a DNA molecule if the particle hits the DNA. The amount of intact DNA remaining in the agarose plugs decreases exponentially for increasing radiation doses or particle fluences. From these curves cross sections for the induction of DSB after heavy ion irradiation have been determined. These results will be discussed in comparison to the results for cell survival.

Argon↗

PubMed1994

Effects of heavy ions on inactivation and DNA double strand breaks in Deinococcus radiodurans R1.

Inactivation and double strand break (dsb) induction after heavy ion irradiation were studied in stationary phase cells of the highly radiation resistant bacterium Deinococcus radiodurans R1. There is evidence that the radiation sensitivity of this bacterium is nearly independent on energy in the range of up to 15 MeV/u for lighter ions (Ar). The responses to dsb induction for charged particles show direct relationship between increasing radiation dose and residual intact DNA.

Argon↗

PubMed1994

Inactivation of individual Bacillus subtilis spores in dependence on their distance to single cosmic heavy ions.

For radiobiological experiments in space, designed to investigate biological effects of the heavy ions of the cosmic radiation field, a mandatory requirement is the possibility to spatially correlate the observed biological response of individual test organisms to the passage of single heavy ions. Among several undertakings towards this goal, the BIOSTACK experiments in the Apollo missions achieved the highest precision and therefore the most detailed information on this question. Spores of Bacillus subtilis as a highly radiation resistant and microscopically small test organism yielded these quantitative results. This paper will focus on experimental and procedural details, which must be included for an interpretation and a discussion of these findings in comparison to control experiments with accelerated heavy ions.

Bacillus subtilis↗

PubMed1994

Inactivation of individual Bacillus subtilis spores in dependence on their distance to single accelerated heavy ions.

In order to understand radiation mechanisms of heavy ions in detail, it is necessary to study effects of single ions on individual biological test objects. Spores of Bacillus subtilis have been used as a suitable small biological test system to measure the inactivation in dependence on the radial distance to the tracks of charged particles. Accelerator experiments have been performed using a modified Biostack technique--biological objects sandwiched between nuclear track detectors. Results of these experiments using ions differing in their energy and atomic number will be discussed under following aspects: (i) methodological differences between the experiments and their possible influences on the results, (ii) common features which are independent on the particle type and energy, (iii) theoretical expectations and problems to find solid theoretical concepts which explain the results.

Argon↗

PubMed1993

Altered ratios of beta-endorphin:beta-lipotropin released from anterior lobe corticotropes with increased secretory drive. II. Repeated stress.

A number of stimuli including acute footshock and electrically-induced seizures lead to release of beta-endorphin immunoreactivity from the anterior pituitary corticotropes. Gel filtration of this beta-endorphin immunoreactivity indicates that approximately 3-fold more beta-endorphin than beta-lipotropin is released into plasma following these acute stressors. A similar preponderance of beta-endorphin over beta-lipotropin is seen in the media of short-term anterior lobe cell suspensions stimulated with ovine corticotropin-releasing hormone. Previous studies indicated that footshock stress, when administered repeatedly, can increase the biosynthesis of anterior lobe proopiomelanocortin (POMC) as indicated by increased steady state adrenocorticotropin/beta-endorphin content as well as increased POMC mRNA levels and increased POMC biosynthesis and rate of processing as measured by pulse-labeling and pulse-chase studies. The goal of the present studies was to determine whether this increased biosynthetic drive results in an alteration in the end products secreted with repeated stress. Acute footshock in a rat which has received 14 days of chronic footshock releases proportionately more beta-lipotropin than is released in a naive rat. Chronic electrically-induced seizures, which also increase anterior lobe POMC derived peptide stores, lead to a similar shift in the ratio of beta-lipotropin:beta-endorphin released following stress. These data suggest that chronic drive and the subsequent changes in POMC peptide stores may lead to a decrease in the proportion of beta-endorphin size immunoreactivity in the releasable pool of the anterior lobe corticotrope, thus altering the hormonal signal from the anterior lobe corticotrope.

Adrenocorticotropic Hormone↗

PubMed1993

Longitudinal assessment of mental development in infants with nonsyndromic craniosynostosis with and without cranial release and reconstruction.

The effect of cranial release and reconstruction on the mental development of infants with nonsyndromic craniosynostosis was evaluated. Longitudinal assessment of mental development for infants before and after cranial release and reconstruction and for infants not undergoing surgical treatment was obtained by using the mental scale of the Bayley Scales of Infant Development. Severity of anatomic craniofacial deformity, perinatal medical risk factors, and age at time of surgery also were investigated. None of the infants displayed mental retardation [Mental Development Index (MDI) score < 70] before or after cranial release and reconstruction. Scores ranged from borderline retardation to very superior following a normal distribution. Severity of anatomic craniofacial deformity and perinatal risk factors were unrelated to mental development. Cranial release and reconstruction did not affect mental development positively or negatively but did result in improvement of the original craniofacial deformity.

Child Development↗

PubMed1989

Cell inactivation, repair and mutation induction in bacteria after heavy ion exposure: results from experiments at accelerators and in space.

To understand the mechanisms of accelerated heavy ions on biological matter, the responses of spores of B. subtilis to this structured high LET radiation was investigated applying two different approaches. 1) By the use of the Biostack concept, the inactivation probability as a function of radial distance to single particles' trajectory (i.e. impact parameter) was determined in space experiments as well as at accelerators using low fluences of heavy ions. It was found that spores can survive even a central hit and that the effective range of inactivation extends far beyond impact parameters where inactivation by delta-ray dose would be effective. Concerning the space experiment, the inactivation cross section exceeds those from comparable accelerator experiments by roughly a factor of 20. 2) From fluence effect curves, cross sections for inactivation and mutation induction, and the efficiency of repair processes were determined. They are influenced by the ions characteristics in a complex manner. According to dependence on LET, at least 3 LET ranges can be differentiated: A low LET range (app. < 200 keV/micrometers), where cross sections for inactivation and mutation induction follow a common curve for different ions and where repair processes are effective; an intermediate LET range of the so-called saturation cross section with negligible mutagenic and repair efficiency; and a high LET range (>1000 keV/micrometers) where the biological endpoints are majorly dependent on atomic mass and energy of the ion under consideration.

Bacillus subtilis↗

PubMed1988

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing.

With chymopapain at a concentration of 10 mg/ml, the authors skin tested 540 chemonucleolysis candidates; six were positive, and 534 were negative. None of the positive patients received therapeutic injections of chymopapain. There were no instances of unequivocal anaphylaxis to chymopapain in the patients with negative skin tests treated with chymopapain. When this 0% incidence of systemic reactions in skin test negative patients is compared with the historical rate of 1%, this difference is statistically significant (p less than 0.05). Restriction of chymopapain treatment to patients with negative prick tests can reduce the incidence of systemic reactions.

Anaphylaxis↗

PubMed1987

CT and MRI of orbital abnormalities in neurofibromatosis and selected craniofacial anomalies.

This article begins with a discussion of normal orbital anatomy and the terminology involved in the description of abnormalities of the orbit. Case reports of patients with neurofibromatosis or with a craniofacial anomaly are presented, and the characteristic orbital findings on both CT and MRI are reviewed. Thus the radiologist's role and the value of CT and MRI in the overall treatment of these often complex abnormalities are elucidated.

Adolescent↗

PubMed1987

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing. A preliminary report.

The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.

Adult↗

PubMed1986

Genetic response of bacterial spores to very heavy ions.

Using spores of two Bacillus subtilis strains differing in repair capacity, we have studied repair and mutation induction in the spores after irradiation with very heavy ions up to uranium with specific particle energies up to 18.6 MeV/u. The results indicate that repair and mutation induction after heavy ion irradiation are closely related to each other and that both phenomena strongly depend on the atomic number and specific energy of the ions. The effects are discussed in comparison with results obtained after X-irradiation.

Bacillus subtilis↗