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Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 127 records · Page 7Linked to original sources

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain.

OBJECTIVE: The objective of this single-center, single-dose, double-blind randomized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels (25 mg or 50 mg) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain. METHODS: The study was designed with a sample size of 69 patients per treatment for a total of 276 patients. However, due to administrative changes at the site, the study was prematurely terminated; thus only 108 patients (26 to 28 patients per treatment), 18 years or older, with severe postepisiotomy pain were randomized to one of the four treatments. Treatments were assessed over a 6-hour period using standard scales for pain intensity and pain relief and a number of derived variables based on these data. Since the study medications were not identical in appearance, the preparation and administration of the study medication, and the observation of the patient, were carried out by two different individuals to maintain double-blind conditions. RESULTS: All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores. The global rating was assessed as "good" or "excellent" by over 75% of the patients in the active treatment groups compared to 7.4% of the patients in the placebo group. Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg. CONCLUSION: Ketoprofen 25 mg or 50 mg, and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery, as well as episiotomy. This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain. All treatments were well tolerated. No adverse events were reported.

Adult↗

[Carotid stenosis--noninvasive diagnosis preferred. Suitability of color-coded duplex ultrasound for preoperative diagnosis].

The high incidence of cerebral ischemic insults caused by atherosclerotic lesions in the carotid artery warrants a careful diagnostic work-up if the therapeutic possibilities now available are to utilized to the full. Until recently, the diagnosis of carotid stenosis was considered the domain of arterial angiography, but MRI angiography and, in particular, color-coded duplex ultrasonography, have now made these techniques so reliable that-as this case report shows--there is no longer any need for routine angiography for surgical planning. Furthermore, even arteriography involving standard projections may fail to provide the necessary information.

Aged↗

Unusual effect of high hydrostatic pressure on basic phospholipase A2 from venom of Agkistrodon Halys Pallas.

The pressure effect on basic phospholipase A2 (BPLA2) from the venom of Agkistrodon Halys Pallas from the Zhe-Jiang province of China was studied by fluorescence spectroscopy from 0.1 to 650 MPa. It was found that the pressure effect on the tryptophan residue fluorescence emission spectra of the enzyme were-was significantly different in two pressure ranges: from 0.1 to 400 MPa and from 400 to 650 MPa respectively. For increasing pressure, the spectrum shifted to the red in the lower pressure range and to the blue in the higher pressure range. Whereas the red shift could be ascribed to the intrinsic pressure dependence of the fluorophore (trp), the blue shift indicated a pressure induced protein conformational change toward a structure where the single tryptophan is in a less polar environment, suggesting its burying deeper inside the protein. This is the first time that such a phenomenon has been observed. Generally, high pressure denaturation of proteins leads to a red shift of tryptophan fluorescence. It was also found that the break point in pressure at which the blue shift began was dependent both on temperature and on the presence of Ca+2 ion, but not on the protein concentration. Experiments at different BPLA2 concentrations and light scattering under pressure indicated that the blue shift was not caused by protein aggregation under high pressure.

Agkistrodon↗

PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells.

To identify genes that are differentially expressed during self-repair processes in mouse brain, we screened a subtracted cDNA library enriched for brain-specific clones. One of these clones, H74, detected a 4.4-kb mRNA predominantly expressed in brain and dorsal root ganglia neurons. Expression increased continuously during the lifespan and the state of differentiation, but decreased after entorhinal-cortex lesion. A full-length cDNA clone was isolated from a cerebellum cDNA library and characterized. Sequence analysis and database search revealed high sequence similarity to FAP52, a protein expressed in focal-adhesion contacts, and uncharacterized Echinococcus and Caenorhabditis elegans gene products. Furthermore, peptide sequences derived from human cDNA fragments showed up to 65% sequence identity at the amino acid level. The presence of a C-terminal src homology 3 (SH3) domain and its phosphorylation by casein kinase 2 (CK2) and protein kinase C (PKC) imply a role in signaling. Here we demonstrate that the gene encodes a phosphoprotein, referred to as PACSIN, with a restricted spatial and temporal expression pattern.

Adaptor Proteins, Signal Transducing↗

Influence of polyols on the structural properties of Kluyveromyces lactis beta-galactosidase under high hydrostatic pressure.

The conformational changes in dimeric Kluyveromyces lactis beta-galactosidase induced by hydrostatic pressure were investigated by means of its intrinsic tryptophan fluorescence. At high pressure, the fluorescence emission spectrum was shifted to the red, indicating the exposure of buried Trp residues to the aqueous solvent. This spectral change was paralleled by a loss of enzyme activity. The shift of the emission spectrum was quantified by evaluating the centre of spectral mass ((nu(g))), which is an intensity-weighted mean wavenumber. The experimental data could be fitted to a two-state transition (native<-->denatured), corrected for a linear pressure dependence of (nu(g)), and allowed the determination of thermodynamic parameters deltaG0(app), V(app) and P(1/2). The results were consistent with a partial unfolding of the protein and not simply with dissociation of this dimeric enzyme. In the presence of polyols, the native conformation of beta-galactosidase was considerably more resistant to pressure. This protective effect of polyols is probably due to a reduced accessibility of water inside the protein structure, through the direct or indirect action of these additives on the enzyme.

Animals↗

Evidence for a new type of outer membrane lipid in oral spirochete Treponema denticola. Functioning permeation barrier without lipopolysaccharides.

A new class of outer membrane lipid (OML) was isolated from the oral spirochete Treponema denticola strain ATCC 33521 using a phenol/chloroform/light petroleum procedure normally applied for lipopolysaccharide extraction. In addition to chemical analysis, Fourier transform infrared (FTIR) spectroscopy was applied to compare the biophysical properties of OML with lipopolysaccharides (LPS) and lipoteichoic acids (LTA). Isolated OML fractions represent 1.4% of the total dry cell weight, are about 4 kDa in size, and contain 6% amino sugars, 8% neutral sugars, 14% phosphate, 35% carbazol-positive compounds, and 11% fatty acids (containing iso- and anteiso-fatty acyl chains). Rare for outer membrane lipids, OML contains no significant amount of 3-deoxy-D-manno-octulosonic acids, heptoses, and beta-hydroxy fatty acids. The fatty acyl chain composition, being similar to that of the cytoplasmic membrane, is quite heterogeneous with anteiso-pentadecanoic acid (12%), palmitic acid (51%), and iso-palmitic acid (19%) as the predominant fatty acids present. Findings of a glycerol-hexose unit and two glycerol-hexadecanoic acid fragments indicate a glycolipid membrane anchor typically found in LTA. There was also no evidence for the presence of a sphingosine-based lipid structure. The results of FTIR measurements strongly suggest that the reconstituted lipid forms normal bilayer structures (vesicles) expressing a high membrane state of order with a distinct phase transition as typical for isolated LPS. However, in contrast to LPS, OML of T. denticola has a lower Tm near 22 degreesC and a lower cooperativity of the phase transition. The results suggest a different kind of permeation barrier that is built up by this particular OML of T. denticola, which is quite different from LPS normally essential for Gram-negative bacteria.

Cell Membrane Permeability↗

Reaction of neuronal nitric-oxide synthase with oxygen at low temperature. Evidence for reductive activation of the oxy-ferrous complex by tetrahydrobiopterin.

The reaction of reduced NO synthase (NOS) with molecular oxygen was studied at -30 degreesC. In the absence of substrate, the complex formed between ferrous NOS and O2 was sufficiently long lived for a precise spectroscopic characterization. This complex displayed similar spectral characteristics as the oxyferrous complex of cytochrome P450 (lambda max = 416.5 nm). It then decomposed to the ferric state. The oxidation of the flavin components was much slower and could be observed only at temperatures higher than -20 degreesC. In the presence of substrate (L-arginine), another, 12-nm blue-shifted, intermediate spectrum was formed. The breakdown of the latter species resulted in the production of Nomega-hydroxy-L-arginine in a stoichiometry of maximally 52% per NOS heme. This product formation took place also in the absence of the reductase domain of NOS. Both formation of the blue-shifted intermediate and of Nomega-hydroxy-L-arginine required the presence of tetrahydrobiopterin (BH4). We propose that the blue-shifted intermediate is the result of reductive activation of the oxygenated complex, and the electron is provided by BH4. These observations suggest that the reduction of the oxyferroheme complex may be the main function of BH4 in NOS catalysis.

Animals↗

Determination of propofol in low-volume samples by high-performance liquid chromatography with fluorescence detection.

In order to determine propofol in rat whole-blood samples of 50 microl, we developed a rapid, simple and reliable method which is characterized by precipitation of blood elements with acetonitrile and submission of the supernatant to HPLC analysis with fluorescence detection. The method described is linear from 0.4 to 40 mg/l and the relative standard deviations in this concentration range are less than 10%. The limit of quantification proved to be 0.4 mg/l. Blood constituents do not interfere with the assay.

Anesthetics, Intravenous↗

Can monomers of yeast enolase have enzymatic activity?

Using a combination of ultraviolet spectroscopy under pressure and stopped-flow kinetics under pressure, we have shown that the monomers of yeast enolase produced by hydrostatic pressure are inactive. K(eq), deltaV and deltaV for the dissociation/inactivation produced by hydrostatic pressure have been determined under various conditions. Removing the Mg2+ from enolase, either by adding EDTA or by preparing apoenzyme, displaces the equilibrium towards monomers and decreases both deltaV and deltaV. Loss of Mg2+ contributes to the negative deltaV for dissociation; this loss occurs, at least partially, in the transition state for dissociation. Both removal of Mg(II) and dissociation of the enzyme produce major changes in the intensity of the aromatic region of the CD spectrum. We propose that these changes in the CD spectra reflect changes in the conformations of the 'mobile loops' of enolase. The precise conformation of these, loops is necessary for binding Mg2+ (and, hence, for activity) and for maintaining subunit interactions.

Circular Dichroism↗

Expression of HSP 70 as a potential prognostic marker for acute rejection in human liver transplantation.

In experimental models, the synthesis of heat shock protein 70 (HSP 70) has been recognized as an intracellular response to ischemia and reperfusion, insults inherent to transplantation. In this study, the HSP response in early stages of human liver transplantation was investigated. HSP 70 mRNA expression was detected by means of reverse transcriptase (RT)-PCR in liver biopsies (n = 28) and in cells obtained from the organ perfusate (n = 14) following cold preservation. The expression of HSP 70 differed substantially between individuals. Retrospective analysis revealed a close correlation of the amount of HSP 70 mRNA in perfusate cells and biopsies with the onset of organ dysfunction due to early graft rejection. Patients with early graft rejection had a significantly lower amount of HSP 70 mRNA than patients without rejection. These results suggest a protective role of HSP 70 expression. Low levels of HSP 70 may, therefore, represent a prognostic marker for early graft rejection.

Adult↗

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure.

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver.

Acute Disease↗

Circulating interleukin-1 receptor antagonist (IL-1RA) serum levels in patients undergoing orthotopic heart transplantation.

In a pilot study we determined the serum levels of circulating interleukin-1 receptor antagonist (IL-1ra) in patients undergoing orthotopic heart transplantation and in control patients scheduled for open heart surgery without allograft transplantation. Blood samples were obtained from 12 transplant recipients and 7 controls prior to the operative procedures to determine baseline values. Serum levels of IL-1ra were measured within 12 h of decrossclamping of the aorta and every 24 h for the following 14 days. Endomyocardial biopsies were obtained weekly for the 1st month after transplantation. Compared to baseline values, IL-1ra serum levels 12 h after decrossclamping of the aorta were significantly higher both in the control group (507 +/- 165 vs 3980 +/- 452 pg/ml, P < 0.01) and among the transplant recipients (413 +/- 180 vs 4117 +/- 459 pg/ml, P < 0.01) IL-1ra levels remained significantly elevated for 2 and 5 days, respectively. There were no significant differences in the IL-1ra serum levels between the two groups throughout the observation period. Endomyocardial biopsies of two patients showed acute allograft rejection, Billingham grade IIIa and IIIb, respectively. In both cases, the rejection episodes were accompanied by a renewed and more pronounced elevation in the IL-1ra serum levels beyond 4000 pg/ml for at least 2 days. These preliminary results indicate that IL-1ra may be a nonspecific immune marker during the first few days after orthotopic heart transplantation and cardiopulmonary bypass. Moreover, renewed, prolonged increases in IL-1ra appear to be associated with rejection. Further studies are needed to confirm the predictive value of IL-1ra in the detection of acute allograft rejection.

Biomarkers↗

[Surgery of acute aortic valve endocarditis: prognosis in paravalvular abscess].

The occurrence of paravalvular abscesses in the course of an acute endocarditis of the aortic valve indicates an advanced stadium of the disease. The infection has spread beyond the limits of the valve leaflets, and ongoing destruction of the paravalvular tissue is to be expected, if the endocarditis is continually treated by antibiotics alone. Surgery of acute endocarditis with paravalvular abscess, however, supposedly carries an increased risk of early mortality and late morbidity. The following prospective study was carried out to determine whether a radical surgical approach together with aggressive postoperative antibiotic therapy could help to improve results. Between 1988 and 1995, 138 patients were operated during the acute phase of infective endocarditis; in 102 the aortic valve was involved. Among these, 44 had paravalvular abscesses at the time of surgery. The mean age of both groups was the same, but there was a higher rate of concomitant coronary artery disease, multiple valve involvement, advanced NYHA-class, and staphylococcal disease among the patients with abscesses. All interventions were carried out with cardiopulmonary bypass and cardioplegic arrest. The aortic valve was resected, abscesses were removed, and each part of potentially infected or necrotic tissue was resected as complete as possible, irrespective of the possibility to jeopardize the conduction system or to create large tissue defects. The aortic valve was replaced with a mechanical prosthesis in each case. The postoperative antibiotic regimen was specifically directed against the microorganisms isolated preoperatively; therapy was only modified, if signs of systemic infection did not disappear three days after surgery. The operative mortality was 10% among patients without an abscess and 11% in patients with a paravalvular abscess. Early recurrent endocarditis was recorded in two patients without and in only one patient with an abscess. Late recurrent endocarditis was noted in three patients; none of them had abscesses at the time of surgery. We conclude that the operative risk of acute endocarditis of the aortic valve with a paravalvular abscess does not have to be inevitably higher compared to cases without paravalvular involvement. To achieve these results, it is necessary to use a radical surgical approach and to adjust postoperative antibiotic therapy, if infectious signs do not disappear shortly after surgery.

Abscess↗

[Emotional status of patients on the waiting list for heart transplantation].

Although heart transplantation is by now considered an established procedure in patients with terminal heart failure, there has been a stagnation or even a decline in the number of transplantations performed due to the decreased willingness of the public to provide organs. As a consequence of this development patients have to wait for a donor organ for a much larger time. The aim of this study was to examine patients especially during this very stressful period. From July 1995 to February 1997, 62 patients who had been continuously added to the waiting list were examined regarding their quality of life and emotional state. Completely assessed were 53 patients (participation rate: 85%). As compared to a healthy control group, patients with terminal heart failure on the waiting list reported their quality of life in the physical as well as the psychological area as significantly lower (p < 0.001). The areas of depression (p < 0.001) and anxiety (p < 0.001) also showed a significant difference. There was an obvious correlation (p < 0.01) between the key symptom of terminal heart failure-- dyspnoea--and the measured level of depression. This served to support the notion that there is a connection between the psychological and the somatic state in these severely ill patients. These results point to the necessity of supportive psychotherapeutic treatment during this very stressful time.

Adult↗

Effect of cysteine substitutions on dimerization and interfragment linkage of human cytomegalovirus glycoprotein B (gp UL55).

Experiments were carried out to analyze the function of cysteine residues at amino acid positions 506 (cI), 550 (cII), 573 (cIII), and 610 (cIV), in dimerization and/or disulfide linkage of human cytomegalovirus (HCMV) glycoprotein B (gB). Single c-codons or pairs were substituted in the gB sequence of constructs which were used for transfection and selection of stable transfectants. Analysis of gB expression products revealed that single substitutions of cIII or cIV, but neither single nor double substitutions of cI or/and cII prevented gB dimerization. All substituted gB derivatives were, however, no longer processed by proteolytic cleavage. After deletion of the membrane anchor domain, correct proteolytic processing was again observed for anchorless gB forms. Substitutions of cI or cI/cII in secretory gB appeared to interfere with disulfide linkage between gB cleavage fragments. In the case of anchorless gB with substitutions of cII, cIII, or cIII/cIV, however, extracellular gB forms were not recovered. Using the Sindbis expression system recovery of all anchorless gB forms with cysteine substitutions was achieved. Analysis verified involvement of cI/II substitutions in intrachain disulfide linkage between cleavage fragments of HCMV gB.

Amino Acid Sequence↗

Remnant-like particle cholesterol levels in patients with dysbetalipoproteinemia or coronary artery disease.

PURPOSE: Several studies have provided support for a proatherogenic role for remnant lipoproteins. Thus, the aim of this study was to compare remnant-like particle (RLP) cholesterol levels in patients with coronary artery disease who were normolipidemic with those in controls of similar age and gender. We also assessed the usefulness of measuring RLP-cholesterol levels in patients with type III dyslipidemia. SUBJECTS AND METHODS: Remnant-like particle cholesterol levels were measured in 63 normolipidemic men with coronary artery disease and 23 male controls of similar age as well as in 15 patients with type III dyslipidemia and 103 controls, using an immunoaffinity method. RESULTS: Remnant-like particle cholesterol levels were significantly increased in men with coronary artery disease compared with controls (7.6 +/- 3.8 mg/dL versus 5.7 +/- 1.9 mg/dL, P < 0.01). In patients with coronary artery disease, RLP-cholesterol levels were correlated with total triglyceride and nonhigh-density-lipoprotein (HDL) cholesterol levels, but not with HDL-cholesterol levels. RLP-cholesterol levels were significantly elevated in patients with type III dyslipidemia (median 119, range 31 to 240 mg/dL) compared with controls (median 5.6, range 2.2 to 10.5 mg/dL, P < 0.001). CONCLUSION: Normolipidemic men with coronary artery disease have increased levels of RLP-cholesterol that is not detected with conventional lipid screening. The RLP-cholesterol assay is a simple method for detecting high concentrations of remnant lipoproteins in patients with type III dyslipidemia.

Adult↗

Operation for infective endocarditis: results after implantation of mechanical valves.

BACKGROUND: Operation for acute endocarditis during the active phase violates a basic surgical rule not to implant a foreign body into an infective process, resulting in a high operative mortality and the risk of early recurrent endocarditis. Several investigators analyzing risk factors for perioperative mortality and morbidity presented strategies for more favorable outcomes, but most studies suffer from the drawback of heterogeneous populations observed over a long period of time. METHODS: We present a prospective study on 138 patients operated on from March 1988 to March 1996. Patients were only included if the activity of the infection was proved by positive culture of the valve leaflets or by histologic staining. During the observation period, indication for operation, surgical approach, and postoperative antibiotic therapy were standardized as much as possible. After radical debridement of all parts of infected tissue, valve replacement was carried out with mechanical prostheses. RESULTS: The early mortality was 11.5% overall. High New York Heart Association functional classification, advanced age, and staphylococcal disease were significant risk factors for early mortality. The site of infection, multiple valve involvement, and prosthetic valve endocarditis did not affect the outcome. Early recurrent endocarditis was recorded in only 3 patients of the entire series. CONCLUSIONS: In case of acute infective endocarditis, valve replacement with mechanical prostheses is a safe procedure, if radical operation and aggressive postoperative antibiotic therapy are performed. For further improvements of the results, earlier operation is advisable in patients with rapidly progressive cardiac deterioration and in most cases of staphylococcal endocarditis.

Acute Disease↗

Temporary atrial electrode for the treatment of supraventricular tachycardia after cardiac operations.

BACKGROUND: Supraventricular tachycardia is a common postoperative complication early after cardiac operations. A temporary atrial patch electrode for low-energy atrial defibrillation was developed in 1992 and subsequently tested. METHODS: The electrode first was tested and removed intraoperatively during open heart operations in 10 patients (phase I). After the intraoperative testing, the temporary atrial patch electrode was implanted in 20 patients for postoperative termination of spontaneous episodes of supraventricular tachycardia (phase II). When supraventricular tachycardia occurred, biphasic shocks (1.2 to 5 J) were applied and the atrial defibrillation thresholds were measured. RESULTS: In phase I, the mean intraoperative atrial defibrillation threshold was 1.6 +/- 1.4 J, with a mean shock impedance of 64 +/- 7.3 omega. In phase II, 6 of 20 patients (30%) had 7 episodes of atrial fibrillation (n = 6) and atrial flutter (n = 1) after operation. In 5 patients, the supraventricular tachycardia could be converted to a sinus (n = 5) or normofrequent atrioventricular rhythm (n = 1). The mean postoperative defibrillation threshold was 2.7 +/- 2.1 J, with a mean shock impedance of 50.2 +/- 6.8 omega. CONCLUSIONS: The temporary atrial patch electrode allows low-energy defibrillation of episodes of atrial fibrillation. It may serve as an alternative therapeutic option for the treatment of supraventricular tachycardia.

Cardiac Surgical Procedures↗