[The Hera women--drug abusing victims of incest].
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Adult↗
Biomedical subjects
O Hoffmann
Publications and source records attributed to O Hoffmann.
Factors predicting pituitary adenoma invasiveness in acromegalic patients.
Forty-four adult acromegalic patients carrying growth hormone-producing pituitary macroadenomas were investigated with neuroradiological and endocrinological techniques. Plasma growth hormone and somatomedin-C levels were repeatedly measured before surgical removal of tumors and during the follow-up period. Twenty-five patients presented preoperatively with an invasive adenoma that involved the cavernous sinus (CS). Diagnosis of tumor invasivity was made according to distinct neuroradiological criteria and was confirmed or rejected during surgery Significantly higher basal growth hormone levels were found in patients with CS invasion than in cases without tumor growth in the CS. Evidence is presented that plasma growth hormone level in acromegalics is a more sensitive indicator for predicting tumor invasiveness than somatomedin-C. Growth hormone basal values before surgery and the extent of their decrease after removal of tumor correlate with adenoma growth in the parasellar compartments and should be used as a prognostic factor to aid in planing adjuvant tumor treatment.
Acromegaly↗
High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.
OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.
Adult↗
Dextromethorphan potentiates morphine antinociception, but does not reverse tolerance in rats.
The N-methyl-D-aspartate (NMDA) and cholecystokinin (CCK)-B receptors may have a role in the development and reversal of tolerance to morphine. In morphine-tolerant rats, addition of the CCK-B receptors antagonist CI 988 or the NMDA receptor blocker dextromethorphan enhanced the antinociceptive effect of morphine on the hot plate test. However, combined administration of CI 988 and dextromethorphan did not further potentiate the antinociceptive effect of morphine in tolerant rats. Dextromethorphan by itself had no effect in tolerant rats. In drug-naive rats, dextromethorphan by itself had no antinociceptive effect, but when combined with morphine or morphine and CI 988, it significantly potentiated the magnitude and duration of the effect of morphine. Thus, unlike the reversal of tolerance with CI 988 at doses that did not potentiate the effect of morphine, the antinociception observed with the NMDA antagonist in the presence of morphine in tolerant rats may not represent the reversal of tolerance, but may instead reflect the potentiation of morphine's analgesic effect by dextromethorphan.
Analgesics, Opioid↗
L-740,093, a new antagonist of the CCK-B receptor, potentiates the antinociceptive effect of morphine: electrophysiological and behavioural studies.
The interaction between morphine and L740,093, a newly developed highly potent antagonist of cholecystokinin-B receptors, was examined in electrophysiological and behavioural studies. Intravenous L740,093 at 0.01 mg/kg had no effect on its own, but significantly potentiated the depressive effect of 1 mg/kg morphine on the nociceptive flexor reflex in decerebrate, spinalized rats. Similarly, subcutaneous L740, 093 at 0.03 mg/kg significantly prolonged the duration of antinociception induced by 10 mg/kg morphine in the rat hotplate test. A bell shaped dose-response curve was noted in the behavioural studies with respect to the interaction between L740,094 and morphine. L740,093, which has excellent CNS penetration, may represent a new tool in studying the involvement of the endogenous cholecystokinin system in the modulation of opioid analgesia and in exploring novel analgesics.
Analgesia↗
N-methyl-D-aspartate receptor antagonists potentiate morphine's antinociceptive effect in the rat.
The interaction between morphine and three antagonists of the N-methyl-D-aspartate (NMDA) receptor. MK-801 (non-competitive channel blocker), dextromethorphan (clinically available non-competitive antagonist) and CGS19755 (competitive receptor antagonist), was examined in rats with the hot plate test. The NMDA antagonists were administered intraperitoneally and none of them caused antinociception at doses that did not produce motor deficits (0.1 mg kg-1 MK-801, 30 mg kg-1 dextromethorphan and 5 mg kg-1 CGS19755). However, pretreatment with the NMDA antagonists at these doses 30 min prior to subcutaneous injection of 5 mg kg-1 morphine significantly potentiated the antinociceptive effect of morphine, with strongest effect observed with dextromethorphan. It is suggested that blockade of NMDA receptors enhances the antinociceptive effect of morphine and NMDA antagonists may improve the analgesic efficacy of morphine in the clinic.
Analgesics↗
Vasomotion, regional cerebral blood flow and intracranial pressure after induced subarachnoid haemorrhage in rats.
The objective of our study was to examine the relation of the intracranial pressure (ICP), cerebral perfusion pressure (CPP), regional cerebral blood flow (rCBF), and vasomotion in the acute phase in rats after having induced subarachnoid haemorrhage (SAH). The experiments were carried out on a total of 21 Wistar rats by means of neuroleptanalgesia and controlled mechanical ventilation. In 16 animals SAH was induced according to the method described by Solomon et al. with a fractionated application of 0.5 ml autologous blood into the cisterna magna. In a control group 0.5 ml of physiological saline solution was injected under identical conditions. The parameters were registered continuously before, during and at least 3 hours after the bolus application. The rCBF and vasomotion were recorded by laser-doppler fluxmetry. The ICP and the systemic arterial blood pressure were registered simultaneously. In the course of the experiment blood gas analyses were carried out regularly for documentary reasons of normoventilation. Our results show that the Cushing-response-after having induced SAH-led to a deterioration of the cerebral perfusion. In the control group however an increase in ICP and rCBF was recorded. The frequency and amplitude of the oscillations of Doppler signals, described as vasomotion, were significantly reduced in the SAH group as compared to the control group (p = 0.0004) during the course of the experiment. After having induced SAH an impairment of the cerebral autoregulation becomes apparent which seems to manifest itself on the level of microvascular structures as a suppressed behaviour pattern of vasomotion. Although basal vessels may constrict distal parenchymal vessels tend to dilate after SAH. The dilation-described as a reduction of vasomotion-could also be measured in clinical situations by means of laserdoppler fluxmetry.
Animals↗
Diagnostic and prognostic significance of anticardiolipin antibodies in patients with recurrent spontaneous abortions.
PROBLEM: The role of ACA in unexplained RSA is controversial. In the present study, diagnostic and prognostic aspects were investigated. METHOD: One hundred five nonpregnant patients with primary, 29 with secondary RSA, and 209 controls were investigated for IgG-ACA. Follow-up studies were done during pregnancy in 76 individuals. IgM-ACA were tested in a subset of patients. RESULTS: Elevated ACA levels were significantly more frequent in both patient groups (26 and 24%) than in controls (16%). However, there was no correlation of ACA with various parameters including pregnancy outcome. In ACA-positive patients with successful pregnancy a significant decrease of ACA values during pregnancy was observed, while ACA remained high in aborting patients. IgG- and IgM-ACA correlated well. CONCLUSIONS: Although the data from nonpregnant RSA patients does not allow diagnostic or prognostic conclusions to be drawn, sequential testing of ACA-positive individuals provides the possibility to foresee pregnancy outcome.
Abortion, Habitual↗
The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats.
The ability of the selective cholecystokinin-B (CCK-B) receptor antagonist Cl 988 to reverse tolerance to morphine's antinociceptive effect was investigated with the hot-plate test in Sprague-Dawley rats. Tolerance was induced by subcutaneous (s.c.) injection of 10 mg kg-1 morphine twice daily for four days. On the fifth day rats were administered CI 988 (10 mg kg-1) or saline plus 5 mg kg-1 morphine s.c. Significant antinociception was observed in the group that received the CCK-B antagonist plus morphine, whereas the saline plus morphine group exhibited total tolerance. These results suggest that upregulation of the endogenous CCK system during repeated morphine administration may have an important role in the development of opiate tolerance.
Analgesia↗
The endogenous ouabain-like sodium pump inhibitor in cold injury-induced brain edema.
An endogenous ouabain-like factor (EOLF) was measured in brain tissue of cats 12 and 24 hrs after cold injury-induced edema. EOLF was assayed via its inhibition of 86Rb+ uptake in human red blood cells in a fraction which was obtained from brain tissue by methanol extraction, chloroform treatment and purification of the water phase by C-18 HPLC. As compared to the contralateral hemispheres with an EOLF concentration of 605 +/- 71 pmol ouabain equivalents per g wet weight, the edematous hemisphere had significantly higher concentrations: 12 hours after cold injury it was 2600 +/- 1762 pmol (p < 0.03) and fell to 857 +/- 160 pmol ouabain equivalents/g wet weight after 24 hrs. Similar kinetics were evident for the EOLF concentrations in cerebrospinal fluid. It is suggested that the increase of EOLF in the edematous brain hemisphere may participate as a mediator in the development of vasogenic brain edema in the disturbance of the sodium metabolism.
Animals↗
Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson's syndrome.
Movement disorders presenting with parkinsonism may share histopathological features with Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by the accumulation of pathological prion protein in brain. To investigate a possible aetiological link between these conditions and Creutzfeldt-Jakob disease, histoblot immunostaining for pathological prion protein was carried out in 90 cases including idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, Steele-Richardson-Olszewski syndrome, corticobasal degeneration, and Pick's disease. Pathological prion protein was identified in four controls with Creutzfeldt-Jakob disease but not in any of the other diseases examined. The findings suggest that an aetiological role for prions in these movement disorders is unlikely. Histoblotting provides a useful method for screening large areas of tissue for the presence of pathological prion protein and may be helpful in the differential diagnosis of difficult cases.
Brain↗
The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part I: Evaluation of test-specific variables.
The aim of this study was to optimize the experimental conditions of the MTT assay for primary cultures of human brain tumors. This assay is based on the mitochondrial reduction of MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) salt to formazan crystals by living cells. Formazan can be quantified spectrophotometrically. This assay measures the antimetabolic and, by using an adequate recovery period for the cells, also the antiproliferative effects of cytotoxic drugs. Our results suggest the following experimental design for its application as an chemosensitivity assay for human brain tumors: 1-h drug exposure followed by a seven days recovery period without drugs. Then tumor cells are incubated 4 hours with 1 mg MTT/ml and final absorbance readings are performed at 550 nm and 630 nm as test and reference wavelengths respectively. In this way, the assay seems to be a reliable and simple method for rapid chemosensitivity testing in human brain tumors.
Antineoplastic Agents↗
The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part II: Evaluation of patient- and drug-specific variables.
In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.
Antineoplastic Agents↗
Long-term prognosis of infratentorial transient ischemic attacks and minor strokes.
BACKGROUND AND PURPOSE: This study was performed to gather information about long-term prognosis after infratentorial transient ischemic attacks and minor strokes and about the factors influencing it. METHODS: We included 226 patients with transient ischemia and 169 patients with a minor stroke of the brain stem/cerebellum consecutively admitted to a neurological department. Medical records and the findings of computed tomography, Doppler ultrasonography, and angiography were evaluated retrospectively. Follow-up information was gathered from the patients and their physicians by questionnaires. Complete follow-up information was available for 381 patients. RESULTS: During a mean follow-up of 3.9 years, 15.7% of the 381 patients suffered a stroke and 6.8% a myocardial infarction; 15% died. Kaplan-Meier estimates revealed a cumulative stroke rate of 5.1% within the first year and a risk of stroke, myocardial infarction, or death of any cause of 9.8%. In a proportional hazards model, the time-dependent risk of stroke was significantly increased by increasing age (p = 0.018), minor stroke (p = 0.0005), hypertension (p = 0.022), previous stroke (p = 0.0006), and carotid artery occlusive disease (p = 0.0065). The probability of stroke, myocardial infarction, or death was influenced by age (p = 0.0001), minor stroke (p = 0.006), diabetes (p = 0.015), previous stroke (p = 0.002), infarct on a computed tomogram (p = 0.041), and carotid artery disease (p = 0.032). CONCLUSIONS: Long-term prognosis after brain stem/cerebellar transient ischemic attacks and minor strokes is significantly influenced by age, diabetes, hypertension, previous stroke, and concomitant carotid artery disease. Patients with transient ischemic attacks have a better prognosis than those with minor stroke.
Cerebellum↗
On the role of cyclic AMP as a mediator of bone resorption: gamma-interferon completely inhibits cholera toxin- and forskolin-induced but only partially inhibits parathyroid hormone-stimulated 45Ca release from mouse calvarial bones.
The effects of gamma-interferon (gamma-IFN) on bone resorption and cyclic AMP formation stimulated by parathyroid hormone (PTH), forskolin, and cholera toxin have been studied in cultured neonatal mouse calvarial bones. Bone resorption was assessed by the release of 45Ca from prelabeled mouse calvarial bone fragments. Cyclic AMP formation was quantified by analyzing the amount of the nucleotide in calvarial bone tissue. gamma-IFN completely blocked the 45Ca release response to forskolin and cholera toxin in 96 h cultures. In contrast, the 45Ca release response to PTH was only partially inhibited, an effect that was seen over a wide range of PTH concentrations. The inhibitory effect of gamma-IFN was dose dependent, with a threshold for action at 10 U/ml. Forskolin-stimulated 45Ca release could only be inhibited when gamma-IFN was added simultaneously with forskolin; gamma-IFN added to bones prestimulated with forskolin had no effect. The inhibitory effect of gamma-IFN on PTH-stimulated 45Ca release was seen first after a time lag of 48 h. In contrast calcitonin caused an inhibition after only 3 h. PTH and cholera toxin stimulation of radioactive calcium release was also inhibited by gamma-IFN in bones treated with indomethacin. gamma-IFN inhibited forskolin-induced 45Ca release in bones treated with the mitotic inhibitor hydroxyurea. No effect of gamma-IFN on cyclic AMP formation induced by PTH, cholera toxin, or forskolin could be seen. These data show that gamma-IFN inhibits forskolin- and cholera toxin-induced bone resorption by a mechanism unrelated to prostaglandin production or mitotic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
HLA typing and lymphocytotoxic crossmatches using conventional techniques or immunobeads. A comparative study.
In a prospectively designed comparative study, HLA class I and class II typing was performed after B/T lymphocyte separation by nylon wool (NIH technique) or using immunomagnetic beads (IMB technique). Samples from 70 healthy individuals (group A) and from 47 patients with potential typing problems (group B) were examined. Complete typing failures occurred more frequently with NIH than with IMB. Except for class I in group A, the rate of correct decisions for antigen assignment was significantly higher with IMB. For class II serum reactions, specificity, predictive value and efficiency were superior for IMB, while sensitivity appeared higher for NIH. This can possibly be explained by a prozone effect which was observed in 9 of 36 titration experiments only with the IMB technique. Correlation of both methods in 104 crossmatches prior to kidney transplantation was poor using peripheral blood lymphocytes, but excellent with spleen cells. In addition to the important advantages of the IMB technique for potential problem cases, especially for class II, typing time is reduced to one third, which is of particular clinical importance in kidney transplantation. However, lymphocytotoxic crossmatches prior to transplantation, if performed by IMB, should be carried out using different serum dilutions or with donor spleen cells instead of peripheral blood lymphocytes.
Antibodies, Monoclonal↗
Experimental considerations on the measurement of prostaglandins during long-time incubations of neonatal mouse calvaria.
The influence of experimental conditions during long-time (72 h) incubations of neonatal mouse calvaria on the measurement of prostaglandins was investigated. Incubations of the cultured calvaria were carried out in the presence and absence of stimulating agents of bone resorption, such as thrombin and parathyroid hormone. It was found that during the first 24 h prostaglandin levels, estimated by gas chromatography negative ion chemical ionization mass spectrometry, did not correlate with calcium liberation, but were merely an artefact resulting from surgery by preparing the calvaria.
6-Ketoprostaglandin F1 alpha↗
Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria.
The bone-resorbing activity of thyroid hormones was evaluated in neonatal mouse calvaria maintained in organ culture for 96 h. Thyroxine (T4) between 10(-8) and 10(-5) mol/liter and triiodothyronine (T3) between 10(-8) and 10(-7) mol/liter caused a dose-dependent release of calcium from cultured bone. The thyroid hormone effect was delayed in onset for at least 24 h, and after 96 h of culture amounted to 50-90% of the bone-resorbing activity of 10(-8) mol/liter parathyroid hormone (PTH). The bone-resorbing action of T4 as well as of T3 was completely blocked by 100 U/ml interferon-gamma (IF-gamma) or 20 mU/ml salmon calcitonin (CT). "Escape" from CT inhibition, which is a well-known phenomenon in the action of PTH, was not observed with thyroid hormone-mediated bone resorption. Thyroid hormone treatment of cultured calvaria resulted in a gradual increase between 48 and 96 h of medium concentrations of prostaglandin (PG) E2 and particularly of 6-keto-PGF1 alpha, the inactive metabolite of prostacyclin (PGI2). The release of PGF2 alpha in general was not significantly affected. Although the effect of thyroid hormones on PG release from cultured calvaria was completely abolished by 5 x 10(-7) mol/liter indomethacin, in some experiments indomethacin reduced thyroid hormone-mediated bone resorption by only 50%. This indicates that thyroid hormone action on bone is also mediated by a PG-independent mechanism.
6-Ketoprostaglandin F1 alpha↗