Biomedical subjects
H Schubert
Publications and source records attributed to H Schubert.
Emergency case. Acute testicular pain.
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Radial head fracture.
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Emergency case. Clavicle fracture.
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Wet-to-dry ratio of lung tissue and surfactant outwash after one-lung flooding.
Unilateral flooding of the lung after intubation with a double-lumen tube enables intraoperative sonography of the lung tissue. The flooding restricts the pulmonary blood stream of the flooded lung in a relevant degree and thus reduces the right-to-left shunt volume. The deficient perfusion of the lung tissue during the flooded phase might cause capillary permeability disorders and secondary oedema development. This can be determined by examination of extravascular lung water (EVLW) after draining and reventilation of the flooded lung. Although one-time unilateral lung flooding must be distinguished from bronchopulmonary lavage, it is interesting to study the effects of flooding on the surfactant system. The wet-to-dry ratio of the lung tissues of 13 female pigs was ascertained at different times following one-lung flooding (1 to 11 weeks). A trend towards an increased wet-to-dry ratio in the previously flooded lung was found only in the tissue samples taken 1 h after reventilation. After only 24 h, the two lungs no longer differed in their wet-to-dry ratio. In six pigs, the phospholipid content of the drained flooding liquid was determined. It was shown that the surfactant loss caused by flooding was maximally 47% of the calculated surfactant pool of the respective lung.
Simulation of lung lesions for validating the sonography of the flooded lung.
The quality of sonography of a unilaterally flooded lung needs to be validated on lesions of different echogenicity, size and subpleural position. Lesions were simulated in 12 young pigs with three different methods. After transbronchial (method 1) or transpleural puncture (method 2), diverse substances were injected into the lung. After 4 weeks, the thorax was opened and the lung flooded for the sonographic location of the lesions. In method 3, pulmonary lesions were simulated in an acute experiment after thoracotomy by transpleural injection or by filling of a Fogarty catheter balloon and were located sonographically. Transbronchial injection of alcohol invariably led to subsegment atelectasis. Only 25% of thoracoscopically controlled transpleural injections produced focal lesions in experiments in which the animals survived. Representative lesions were found only after alcohol injections. Transpleural injection of blood or a blood/Echovist suspension (method 3) simulated isoechogenic or echo-rich lesions with indistinct boundaries. By filling a Fogarty catheter balloon with saline solution or Echovist suspension, we succeeded in simulating echo-free or echo-rich lesions with smooth contours, located in different subpleural depths. After unilateral lung flooding, sonography successfully detected the locations of all these lesions and revealed their correlation with functional structures. Sonography of the flooded lung might be helpful in the intraoperative location of lesions, especially in the context of video-assisted thoracoscopic surgery.
Hemodynamics and gas exchange during experimental one-lung fluid flooding in pigs.
One-sided fluid flooding of the lung after intubation with a double-lumen tube facilitates pulmonary sonography during surgery. Arterial blood pressure, cardiac index, and heart rate remained unchanged during one-lung fluid flooding in healthy animals. The arterial PO(2) was greater by about 100 mmHg after flooding one lung with 15 ml/kg fluid and ventilation with a FiO(2) of 1.0 compared with total atelectasis. This seems to be identical to a continuos positive airway pressure level of 5 cm H(2)O with pure oxygen on the nonventilated lung. The one-sided fluid flooding induced a statistically significant increase in pulmonary artery pressures and pulmonary capillary wedge pressure. In comparison with total atelectasis, fluid flooding in tendency reduced the pulmonary right-left shunt and increased the arterial PO(2).
Glycosylphosphatidylinositol-specific phospholipase D in blood serum: is the liver the only source of the enzyme?
In cases of systemic inflammatory response syndrome, sepsis, and septic shock, the activity of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in serum amounts to 20 to 25% of the activity found in a healthy control group. The activity of serum GPI-PLD is positively correlated with inflammatory markers and counts of monocytes and stab cells (bands) and negatively correlated with polymorphonuclear neutrophils and lymphocytes in severe diseases. This indicates a yet unknown involvement of the inflammatory system in GPI-PLD liberation and suggests that the liver is not the only source of the plasma enzyme. Plasma was shown to contain an effective inhibitor of GPI-PLD which is soluble in organic solvents. Its concentration in capillary plasma is 20-fold higher than in venous plasma. To find possible other sources of plasma GPI-PLD besides the liver, the GPI-degrading activity was measured in different organs of the rat. Product formation was analysed using [125I]TID-labeled GPI-AP.
Lung flooding--a new method for complete lung sonography.
A sonographic examination of the lung has so far been impossible because of sound reflection. In conjunction with video-assisted thoracoscopic surgery, lung sonography would be helpful to make up for the lack of direct palpation. Animal experiments with pigs were performed to find out whether lung sonography becomes possible following bronchoalveolar flooding with a suitable liquid. The lung was filled with whole electrolyte solution through the left leg of a double-lumen endotracheal tube after resorption atelectasis (method 1) or compressive atelectasis (method 2). As an alternative, liquid perfluorocarbon was used (method 3). Under atelectasis, the lung thus flooded was investigated by ultrasound applied transpleurally and endobronchially. The first results proved that lung flooding is possible if certain prerequisites are fulfilled. Perfluorocarbon flooding led to total sound absorption which prevented sonography, whereas flooding with whole electrolyte solution made complete lung sonography possible, making visible the intrapulmonary vessels, bronchi and peribronchial lymphatic nodes. Measurements proved that the unilateral flooding caused no significant changes in the arterial and central venous pressure nor in transcutaneous oxygen saturation.
[Accumulation of radioactivity in the lung after 111In-octreotide scintigraphy].
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Mutation of a gene encoding a putative glycoprotease leads to reduced salt tolerance, altered pigmentation, and cyanophycin accumulation in the cyanobacterium Synechocystis sp. strain PCC 6803.
The salt-sensitive mutant 549 of the cyanobacterium Synechocystis sp. strain PCC 6803 was genetically and physiologically characterized. The mutated site and corresponding wild-type site were cloned and partially sequenced. The genetic analysis revealed that during the mutation about 1.8 kb was deleted from the chromosome of mutant 549. This deletion affected four open reading frames: a gcp gene homolog, the psaFJ genes, and an unknown gene. After construction of mutants with single mutations, only the gcp mutant showed a reduction in salt tolerance comparable to that of the initial mutant, indicating that the deletion of this gene was responsible for the salt sensitivity and that the other genes were of minor importance. Besides the reduced salt tolerance, a remarkable change in pigmentation was observed that became more pronounced in salt-stressed cells. The phycobilipigment content decreased, and that of carotenoids increased. Investigations of changes in the ultrastructure revealed an increase in the amount of characteristic inclusion bodies containing the high-molecular-weight nitrogen storage polymer cyanophycin (polyaspartate and arginine). The salt-induced accumulation of cyanophycin was confirmed by chemical estimations. The putative glycoprotease encoded by the gcp gene might be responsible for the degradation of cyanophycin in Synechocystis. Mutation of this gene leads to nitrogen starvation of the cells, accompanied by characteristic changes in pigmentation, ultrastructure, and salt tolerance level.
Presumed choroidal granuloma with vitreous hemorrhage resembling choroidal melanoma.
This report describes a presumed choroidal granuloma with vitreous hemorrhage resembling choroidal melanoma. A healthy 31-year-old man, who had progressive vision loss in the right eye during 1 month, was found to have a yellow-white juxtapapillary choroidal mass. Fluorescein angiography demonstrated a choroidal neovascular membrane over the lesion. There was focal persistent hypofluorescence in the late phase of fluorescein angiography. The thickness of the lesion increased from 3.0 mm to 7.1 mm during 1 month. Subretinal and vitreous hemorrhage developed. The patient was suspected to have a choroidal granuloma and choroidal neovascular membrane, and was treated with oral steroids. Ten months later, the vitreous blood cleared completely with an attached retina. Control of inflammation may have a role in the treatment of idiopathic choroidal granulomas and some choroidal neovascular membranes secondary to ocular inflammation.
Disruption of a Synechocystis sp. PCC 6803 gene with partial similarity to phytochrome genes alters growth under changing light qualities.
A gene that may encode a novel light sensing histidine protein kinase, designated plpA (phytochrome-like protein), was isolated from the cyanobacterium Synechocystis sp. PCC 6803. The 200 COOH-terminal amino acids of the gene product show homology with conserved domains of several bacterial histidine kinases and the ethylene response gene etr1 of Arabidopsis, whereas its central region is similar to the chromophore attachment site of plant phytochromes. Interruption or partial deletion of plpA yielded mutants unable to grow under blue light.
Scanning slit confocal microscopy of fungal keratitis.
In vivo scanning slit confocal microscopy was performed in a patient with Fusarium solani keratitis. Morphologically distinctive abundant filamentous structures were observed intrastromally. Confocal microscopy of the culture plate growing F solani from the patient's corneal scraping revealed filaments morphologically similar to the filaments observed in vivo. After 1 week of medical therapy, subsequent confocal microscopy showed an increased load of filaments, supporting the decision to perform a penetrating keratoplasty. Confocal microscopy confirmed that all of the fungus was eradicated. This aided in the decision to administer corticosteroids and quickly discontinue antifungal agents.
Effect of dimethoate on photosynthesis and pigment fluorescence of Synechocystis sp. PCC 6803.
The organophosphorus (OP) insecticides are powerful inhibitors of esterases, and their toxic actions are commonly explained in terms of acetylcholinesterase (EC 3.1.1.7) inhibition but their phytotoxic effects remain unexplained. In this study the effects of an OP insecticide, dimethoate, on cyanobacterial photosynthesis and respiration were measured using the cyanobacterium Synechocystis sp. PCC 6803 as test organism. The insecticide caused enhancement of respiratory O2 consumption at all tested concentrations (10-300 microM) while photosynthesis was found to be significantly affected at concentrations > or = 50 microM. From fluorescence emission analysis, oxygen exchange measurement, and determination of 14CO2 incorporation, it was found that dimethoate caused inhibition of photosynthetic electron transport, resulting in increase of PS II fluorescence and reduction in photosynthetic carbon fixation. An increase of nonphotochemical quenching was caused by the insecticide through the increase in acidity of the thylakoid lumen. Furthermore, detachment of phycobilisomes (PBS) from the PS II reaction centers was observed in terms of increase in PBS fluorescence in treated cultures. This detachment is expected to be caused by membrane fluidity changes. The fluorescence enhancement of PS II was more than that of the PBS.
Risperidone in the treatment of schizophrenia: results of a study of patients from Germany, Austria, and Switzerland.
Results of a subanalysis of data from the multinational risperidone trial (RIS-INT-2) are reported. Patients with chronic schizophrenia were treated with risperidone at 1 mg/day (n = 25), 4 mg/day (n = 27), 8 mg/day (n = 29), 12 mg/day (n = 31), or 16 mg/day (n = 29), or 10 mg/day of haloperidol for 8 weeks. According to the Positive and Negative Syndrome Scale (PANSS) total and subscale scores, improvements were noted in each treatment group from baseline to treatment endpoint. On each scale the magnitude of improvement was greater in the risperidone patients than in the haloperidol patients. The onset of action of risperidone was faster than haloperidol. By treatment week 2, over half of the patients receiving > or = 4 mg/day of risperidone were clinically improved (> or = 20% reduction in total PANSS scores). This rate of improvement was not seen until week 6 in the haloperidol patients. Severity of extrapyramidal symptoms (scores on the Extrapyramidal Symptom Scale) was significantly lower in patients receiving 1 or 4 mg/day of risperidone than in patients receiving higher risperidone doses and in haloperidol patients. The optimal dose of risperidone, in terms of both efficacy and safety, was 4 mg/day. These results confirm the findings of the controlled trials of risperidone conducted in North America and the multinational trial.
Airborne contact dermatitis due to methylchloro- and methylisothiazolinone (MCI/MI).
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PK/PD simulations as a tool for rational design of clinical dosage regimens: an example with Fradafiban.
In clinical studies, pharmacodynamic effects should be achieved, e.g. maintenance of certain effects with reversibly acting drugs. Available data base for early phase II studies is frequently kinetics in healthy volunteers from phase I studies and pharmacodynamic effects from in vivo or ex vivo data. Using the fibrinogen receptor antagonist Fradafiban as an example, a procedure to achieve rational dosage regimens is described. Applied methods were: curve fitting of plasma concentrations obtained in phase I studies, correlation of fibrinogen receptor occupancy (FRO) to plasma concentrations using a sigmoid Emax model with Hill coefficient for PK/PD correlation, simulation of time course of FRO for various dosage regimens, using estimates for variability from PK and PD data in order to estimate not only mean values but also expected range of FRO. In a phase II study with Fradafiban administered intravenously, therapeutically active plasma levels had to be achieved rapidly and maintained over 24 hours employing a simple infusion regimen in 20 patients and 3 dose groups. For the target dose, a FRO of 80% should be achieved in most patients. Using the tools mentioned above, a rapid initial infusion rate of 10 mg over 30 minutes, followed by a maintenance infusion of 30 mg for the remaining 23.5 hours for the target dose resulted in a median predicted FRO of 82%. For the lower dose, a 5/15 mg infusion over 0.5/23.5 hours, achieving a predicted FRO of 68% was used and the upper dose (15/45 mg) resulted in 87% FRO. Median experimental results were 84% FRO for the target dose and 73% and 88%, respectively, for the lower and upper dose. As these results fit reasonably well to the predictions, it can be concluded that kinetics in the mostly elderly patients is similar to kinetics in healthy young volunteers. Furthermore, FRO in patients is nearly identical to that in spiked human plasma. Taken together, it could be proven that PK/PD methods are a useful tool for design of clinical studies of Fradafiban.