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Biomedical subjects

J Lutz

Publications and source records attributed to J Lutz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Non-invasive evaluation of the location, the functional integrity and the oxygen supply of implants: 19F nuclear magnetic resonance imaging of perfluorocarbon-loaded Ba2+-alginate beads.

19F nuclear magnetic resonance imaging (MRI) can be used as a non-invasive tool to simultaneously determine the location, the integrity and the oxygen supply of Ba2+-alginate implants. This requires that the beads (implants) are pre-loaded with the perfluorocarbon compound F-44E. Implantation of solid 19F-labelled beads into the peritoneum, below the kidney capsule or into the muscle of Wistar WU rats demonstrated that these beads could be detected by 19F-MRI for up to 18 months after implantation. This indicated that F-44E is not considerably released from the beads during implantation. The signal to noise ratio of liquid-core beads was higher by a factor of 4 than the signal to noise ratio of solid beads, but liquid-core beads were more fragile and also too large for implantation under the kidney capsule and into the intramuscular tissue. Quantitative 2-dimensional 19F-T1 maps (resolution 0.5 x 0.5 mm) could be deduced from 19F-MRI measurements. These T1-maps correlated to the local pO2-values. The partial oxygen pressure estimated in F-44E-loaded Ba2+-alginate beads showed that the oxygen supply inside the beads was very poor when they were implanted below the kidney capsule or into the peritoneal cavity. These low pO2-values obtained for the renal subcapsular site and the peritoneum may explain the failure of previous immunoisolated islet transplantation studies using these locations.

Alginates↗
PubMed2000

Angiographic and clinical follow-up of percutaneous revascularization for transplant coronary artery disease.

BACKGROUND: There are limited data on the use of percutaneous revascularization techniques for transplant coronary artery disease (CAD). METHODS: Medical records and angiographic results for cardiac transplant patients undergoing percutaneous revascularization at Emory University Hospital were reviewed. Procedural results, results of angiography 4Eth 6 months after intervention, and clinical follow-up were recorded. RESULTS: Nineteen patients underwent 51 interventions. Thirty-eight lesions (75%) were de novo and 13 (25%) were restenotic. All patients had hypertension, 37% had diabetes, 79% had elevated lipid levels, and 53% had at least one episode of moderate to severe allograft rejection (grade 3A or greater). The primary procedural success rate was 100% with no major complications. Six-month restenosis rate (defined as > 50%) was 49%. At 23+/-17 months follow-up, 6 patients were dead or retransplanted (31%). Thirteen patients were alive without retransplantation (9 New York Heart Association class I, 3 class II, 1 class III). CONCLUSION: Percutaneous revascularization is safe and has a high initial procedural success rate in patients with transplant CAD. However, the restenosis rate in this population remains higher than reported for atherosclerotic coronary disease and the long-term prognosis remains poor.

Adult↗
PubMed1999

19F-MRI in vivo determination of the partial oxygen pressure in perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity and different tissues.

Semipermeable hydrogels formed with a biocompatible alginate solution and Ba(2+) ions protect encapsulated cells and tissues from a foreign immune system. For the viability and metabolic activity of the encapsulated materials, a sufficient oxygen supply inside the capsules is necessary. Quantitative (19)F-MRI was performed on perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity, the musculus quadriceps femoris, and beneath the kidney capsule of rats, in order to determine in vivo the partial oxygen pressure (pO(2)) inside the capsules at these implantation sites. The temporal behavior of the pO(2) values was observed for at least 3 months. The most stable values over time were observed in the kidney, where inter-rat pO(2) differences were considerable. In the muscle, the values were very high directly after implantation and decreased to nearly zero after 2 weeks. In the peritoneal cavity, values changed randomly over a wide range between different rats and over time. Magn Reson Med 42:1039-1047, 1999.

Alginates↗
PubMed1999

Effects of systemically applied allopurinol and prednisolone on experimental autoimmune uveitis.

PURPOSE: To compare the effects of allopurinol to those of prednisolone on the oxidative tissue damage and inflammatory response in experimental autoimmune uveitis (EAU). METHODS: Experiments were performed using 27 male Lewis rats. EAU was induced by means of crude retina extract, Freund's adjuvant and pertussis toxin. One group of animals served as controls and two groups were treated systemically, one with allopurinol and one with prednisolone. At the end of the experiments lipid peroxides (LPO), myeloperoxidase activity (MPO), and histological changes were determined in the retinal tissue. LPO were measured by two different methods [thiobarbituric acid reactive substances (TBARS) and malondialdehyde-like substances]. RESULTS: Allopurinol led to a significant reduction in LPO and MPO levels. The steroid treatment also resulted in a significant reduction in MPO activity but LPO were significantly reduced only when measured as TBARS. Histological changes were significantly reduced by allopurinol only. DISCUSSION: Allopurinol is more effective than prednisolone in treating EAU. Its efficacy can be explained by the antioxidative/antiinflammatory and probably immunological action. The antiinflammatory effects of prednisolone are not sufficient to reduce the tissue damage. Allopurinol promises to be a useful alternative to steroids in the treatment of uveitis.

Allopurinol↗
PubMed1999

Developmental changes in response to subatmospheric pressure loading of the upper airway.

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve (S(PF)) was used to characterize upper airway function. We found that S(PF) was flatter in children than in adults (8 +/- 5 vs. 30 +/- 18 ml x s(-1). cmH(2)O(-1), P < 0.002) and that S(PF) correlated with age (r = 0.62, P < 0.01) and body mass index (r = 0. 63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with S(PF) (r = -0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.

Adolescent↗
PubMed1999

Response to inspiratory resistive loading during sleep in normal children and children with obstructive apnea.

The response to inspiratory resistance loading (IRL) of the upper airway during sleep in children is not known. We, therefore, evaluated the arousal responses to IRL during sleep in children with the obstructive sleep apnea syndrome (OSAS) compared with controls. Children with OSAS aroused at a higher load than did controls (23 +/- 8 vs. 15 +/- 7 cmH(2)O. l(-1). s; P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs. non-REM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 +/- 17% of baseline at an IRL of 15 cmH(2)O. l(-1). min; P < 0.001) and after 3 min of IRL (67 +/- 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Despite compensatory changes in respiratory timing, normal children have a decrease in minute ventilation in response to IRL during sleep. However, arousal occurs before gas-exchange abnormalities.

Airway Resistance↗
PubMed1999

Endothelin-1- and endothelin-receptors in lung biopsies of patients with pulmonary hypertension due to congenital heart disease.

Endothelin-1 (ET-1), with its vasoconstrictive and proliferation-stimulating effects, could play a role in the pathogenesis of primary pulmonary hypertension. We investigated the relationship between the ET-1 like immunoreactivity and the ET-receptor density, the grade of the pulmonary vasculopathy, and properties of the pulmonary circulation in patients with pulmonary hypertension due to congenital heart disease. Twenty-six patients with a median age of 1 year and 1 month (6 weeks - 17 years - 9 months) were assigned to group I (n = 15) with a pulmonary to systemic flow ratio (Qp/Qs) > or = 1.5 and a pulmonary to systemic resistance ratio (Rp/Rs) < or = 0.3 ("high flow - low resistance group") and to group II (n = 11) with a Qp/Qs < 1.5 and an Rp/Rs > 0.3 ("low flow - high resistance group"). Patients belonging to group II showed a higher ET(A)-receptor density in lung arteries (p < 0.05) and parenchyma (p < 0.01) than patients in group I. Patients with the highest ET-1 like immunoreactivity in lung artery walls also showed a trend towards a higher ET(A)-receptor density. The ET(B)-receptor expression was low and not related to any of the above factors. Our results suggest that the paracrine lung ET-1 system is up-regulated in pediatric patients with secondary pulmonary hypertension associated with congenital heart disease.

Adolescent↗
PubMed1999

Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation.

BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.

Acute Kidney Injury↗
PubMed1998

[Oxygen treatment methods--a critical analysis of established and controversial procedures (II)].

All diseases related to chronic or intermittent hypoxaemia can be efficaciously treated with the conventional oxygen therapy. The effectiveness of alternative oxygen therapies (oxygen multistep therapy, intravenous oxygen insufflation, haematogen oxidation therapy and ultraviolet blood radiation) has not been proved for any of the alleged numerous indications. Hyperbaric oxygen therapy can be tried, in single cases, outside of its internationally recognized indications, for the treatment of acute hypoxy of the inner ear.

Complementary Therapies↗
PubMed1998

Residue-specific bioincorporation of non-natural, biologically active amino acids into proteins as possible drug carriers: structure and stability of the per-thiaproline mutant of annexin V.

Residue-specific bioincorporation of 1,3-thiazolidine-4-carboxylic acid [thiaproline, Pro(S)], a non-natural amino acid analog of proline, into human recombinant annexin V was achieved with a proline-auxotrophic Escherichia coli strain by fermentation procedures in minimal medium. Quantitative replacement of proline with thiaproline was confirmed by mass-spectrometric, amino acid, and x-ray crystallographic analyses. The wild-type protein and its per-Pro(S) mutant were found to crystallize isomorphously and to show identical three-dimensional structures in crystals. In solution the dichroic properties of the wild-type and per-Pro(S) protein confirmed nearly identical overall folds. From thermal denaturation experiments, however, a reduced Tm (-4.5 K) value was determined whereas the van't Hoff enthalpy and entropy were not significantly affected. Therefore, protein mutants containing bioactive amino acid analogs like thiaproline at multiple sites would be expected to fully retain their functional properties, including immunogenicity, and thus could serve as promising vehicles for targeted drug delivery.

Annexin A5↗
PubMed1998

Effects of perfluorooctylbromide and vitamin E on ischemia induced retinal oxidative tissue damage.

The aim of this study was to investigate the extent to which ischemia and reperfusion lead to oxidative damage of the retinal tissue and investigate how ischemic and reperfused retinal tissues react to the application of perfluorooctylbromide (PFOB) and, if this reaction can be influenced by protective drugs such as vitamin E (Vit.E). The experiments were performed with 60 male Wistar rats, divided into 12 groups using an established model of reversible ischemia and reperfusion of the globe. Grouping of animals was carried out according to different ischemia and reperfusion periods and different therapeutic regimens (PFOB, Vit.E). Treatment with PFOB and/or Vit.E was performed after 60 min of ischemia with 60 min of reperfusion. At the end of the experiments thiobarbituric acid reactive substances (TBARS) were determined in the retinal tissues and served as parameters of oxidative tissue damage. Ischemia of up to 60 min led to a significant increase in TBARS values. Ninety and 120 min of ischemia led to no further significant elevation compared to the 60 min or 90 min group. Following 60 min of ischemia, a reperfusion period of 15 min led to an increase in TBARS values that was significant (P<0.05) after 30 and 60 min. Addition of PFOB resulted in a further significant (P<0.05) increase in TBARS values as compared to the respective group without treatment. Vit. E alone did not change the values significantly compared to the respective group without treatment. However, the application of Vit.E in addition to PFOB led to a significant reduction in TBARS values. Ischemia resulted in severe oxidative retinal tissue damage, which increased during reperfusion. The reperfusion damage might be due to the known depletion of protecting substances such as vitamin E. Enhancement of oxygen supply by PFOB during reperfusion without any tissue protection leads to more severe damage. Thus, additional protection of the tissue by powerful antioxidants is necessary when providing oxygen for better tissue recovery.

Animals↗
PubMed1998

Effects of different perfluorochemicals on dorsal root ganglion cells in vitro.

BACKGROUND: Investigation of the effects of different perfluorochemicals (PFC) on cultured dorsal root ganglion (DRG) cells. METHOD: DRG cell cultures from 9- to 11-day-old chicken embryos were exposed to emulsified perfluorodecalin (PFD; C10F18; 0.5%, 1% and 10%) or perfluorooctylbromide (PFO; C8F17Br; 0.5%, 1% and 10%). The cells were evaluated under phase-contrast optics after 30 h and 120 h for 0.5 and 1% and after 5 h for 10%. To study the integrity of neuronal cells, immunohistochemical labelling for neurofilaments (NF) and tubulin (TUB) was performed. RESULTS: Concentrations of 0.5% and 1% of PFD or PFO did not change immunohistochemical labelling of DRG cells. Co-cultured macrophages showed a foam cell response, presumably representing ingested PFC. At both concentrations PFD induced a weaker foam cell response than PFO. A concentration of 10% led to the death of DRG cells and macrophages within 5 h. CONCLUSION: PFC caused a dose-dependent damage of neuronal cells. Co-cultured macrophages developed a foam cell response similar to that observed in vivo after prolonged presence of PFC in the vitreous body. These observations indicate that PFD and PFO may not be suitable for long-term vitreous replacement in vitreoretinal surgery. However, the model is limited by several factors: (1) there are physiological differences between DRG cells and retinal ganglion cells; (2) in vivo retinal ganglion cells are protected by the overlying tissues; (3) the PFC used in tissue culture must be emulsified.

Animals↗
PubMed1998

Arousal and ventilatory responses during sleep in children with obstructive sleep apnea.

Abnormal central regulation of upper airway muscles may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We hypothesized that this was secondary to global abnormalities of ventilatory control during sleep. We therefore compared the response to chemical stimuli during sleep between prepubertal children with OSAS and controls. Patients with OSAS aroused at a higher PCO2 (58 +/- 2 vs. 60 +/- 5 Torr, P < 0.05); those with the highest apnea index had the highest arousal threshold (r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responses were similar between patients with OSAS and controls; however, the sample size was small. We conclude that children with OSAS have slightly blunted arousal responses to hypercapnia. However, the overall ventilatory and arousal responses are normal in children with OSAS, indicating that a global deficit in respiratory drive is not a major factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in ventilatory control may exist.

Arousal↗
PubMed1997

Lipogastrins as potent inhibitors of viral fusion.

The rate and extent of membrane fusion is markedly sensitive to membrane interfacial properties. Lipopeptides with hydrophilic peptide moieties will insert into membranes, leaving the peptide portion at the membrane-water interface. In this work, we have used a lipopeptide composed of the peptide [Nle15]-gastrin-(2-17)-amide covalently linked to 1,2-diacyl-3-mercaptoglycerol-N(alpha)-maleoyl-beta-alanine to give DM-gastrin or DP-gastrin having 14 or 16 carbon atom acyl chains, respectively. The fluorescence emission from the two Trp residues of these lipopeptides exhibited little or no blue shift upon addition of liposomes of egg-phosphatidylethanolamine containing 5 mol% G(D1a). Iodide quenching of DP-gastrin fluorescence was also independent of lipid. These results indicate that the peptide moiety is exposed to the aqueous environment even though the lipopeptide is firmly anchored to the membrane. Both DM and DP-gastrin markedly raise the bilayer to hexagonal phase transition temperature of dipalmitoleoyl phosphatidylethanolamine. However, DM-E5 lowers this phase transition temperature. These lipopeptides have effects on the overall fusion of Sendai virus to liposomes in accord with their opposite effects on lipid curvature. The lipogastrins are potent inhibitors of viral fusion, while DM-E5 slightly promotes this process. Truncated forms of DM-gastrin are also inhibitory to viral fusion, but are less inhibitory than the full lipopeptide. Analysis of the fusion kinetics shows that DP-gastrin causes a reduction in the final extent of fusion and a marked lowering of the fusion rate constant. Binding of Sendai virus to the ganglioside receptor-containing liposomes was not affected. Consideration of the various contributions to the mechanism of inhibition of viral fusion suggests that effects of lipogastrin on membrane intrinsic monolayer curvature is of primary importance.

Amino Acid Sequence↗
PubMed1997

Nonviral gene delivery to the rat kidney with polyethylenimine.

The aim of this study was to establish a nonviral method for gene delivery to the rat kidney. To this purpose, a panel of reagents was tested, including a monocationic lipid, DOTAP, a polycationic lipid, DOGS (or Transfectam), and three different forms of the cationic polymer polyethylenimine (PEI). A comparison among these compounds was performed in vivo, using luciferase as reporter gene. Complexes containing 10 microg of DNA were injected into the left renal artery of rats and allowed to remain in contact with the kidney for 10 min. Forty-eight hours later, luciferase expression levels in kidney extracts were measured. Kidneys injected with DNA complexed to the branched, 25-kD PEI polymer (PEI 25k) yielded activity levels significantly higher than control, sham-operated kidneys (2.7 x 10(4) vs. 5.2 x 10(3) RLU/kidney, respectively), whereas the other transfecting agents did not yield significant activity over controls. PEI 25k was therefore chosen for further optimization of transfection conditions. Dose-dependent luciferase expression was shown for 10, 50, and 100 microg of PEI-complexed DNA, reaching maximal levels of 2.4 x 10(5) RLU/kidney at 100 microg DNA. The optimal PEI nitrogen/DNA phosphate molar ratio was 10 equivalents. Luciferase activity peaked at 2 days, was still significantly higher than controls at 7 days, and was undetectable at 14 days post-injection. Using beta-galactosidase (beta-Gal) as a reporter, transgene expression was localized almost exclusively in proximal tubular cells.

Animals↗