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Biomedical subjects

R Busse

Publications and source records attributed to R Busse.

At least 109 records · Page 6Linked to original sources
PubMed1997

Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators.

1. We studied the effects of 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) on the activity of purified soluble guanylyl cyclase (sGC), the formation of guanosine-3':5' cyclic monophosphate (cyclic GMP) in vascular smooth muscle cells (VSMC), and on the tone of rabbit isolated aortic rings preconstricted by phenylephrine (PE). In addition, we assessed the combined effect of YC-1, and either NO donors, or superoxide anions on these parameters. 2. YC-1 elicited a direct concentration-dependent activation of sGC (EC50 18.6 +/- 2.0 microM), which was rapid in onset and quickly reversible upon dilution. YC-1 altered the enzyme kinetics with respect to GTP by decreasing KM and increasing Vmax. Activation of sGC by a combination of sodium nitroprusside (SNP) and YC-1 was superadditive at low and less than additive at high concentrations, indicating a synergistic activation of the enzyme by both agents. A specific inhibitor of sGC, 1H-(1,2,4)-oxdiazolo-(4,3-a)-6-bromo-quinoxazin-1-one (NS 2028), abolished activation of the enzyme by either compound. 3. YC-1 induced a concentration-dependent increase in intracellular cyclic GMP levels in rat cultured aortic VSMC, which was completely inhibited by NS 2028. YC-1 applied at the same concentration as SNP elicited 2.5 fold higher cyclic GMP formation. Cyclic GMP-increases in response to SNP and YC-1 were additive. 4. YC-1 relaxed preconstricted endothelium-denuded rabbit aortic rings in a concentration-dependent manner (50% at 20 microM) and markedly increased cyclic GMP levels. Relaxations were inhibited by NS 2028. A concentration of YC-1 (3 microM), which elicited only minor effects on relaxation and cyclic GMP, increased the vasodilator potency of SNP and nitroglycerin (NTG) by 10 fold and markedly enhanced SNP- and NTG-induced cyclic GMP formation. 5. Basal and YC-1-stimulated sGC activity was sensitive to inhibition by superoxide (O-2) generated by xanthine/xanthine oxidase, and was protected from this inhibition by superoxide dismutase (SOD). YC-1-stimulated sGC was also sensitive to inhibition by endogenously generated (O-2 in rat preconstricted endothelium-denuded aortic rings. Relaxation to YC-1 was significantly attenuated in aortae from spontaneously hypertensive rats (SHR), which generated O-2 at a higher rate than aortae from normotensive Wistar Kyoto rats (WKY). SOD restored the vasodilator responsiveness of SHR rings to YC-1. 6. In conclusion, these results indicate that YC-1 is an NO-independent, O-2-sensitive, direct activator of sGC in VSMC and exerts vasorelaxation by increasing intracellular cyclic GMP levels. The additive or even synergistic responses to NO-donors and YC-1 in cultured VSMC and isolated aortic rings apparently reflect the direct synergistic action of YC-1 and NO on the sGC. The synergism revealed in this in vitro study suggests that low doses of YC-1 may be of therapeutic value by permitting the reduction of nitrovasodilator dosage.

Animals↗
PubMed1997

ACE inhibitor potentiation of bradykinin-induced venoconstriction.

1. Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular effects not only by preventing the formation of angiotensin II (AII), but also by promoting the accumulation of bradykinin in or at the vessel wall. In addition, certain ACE inhibitors have been shown to augment the vasodilator response to bradykinin, presumably by an interaction at the level of the B2 receptor. We have investigated whether this is a specific effect of the ACE inhibitor class of compounds in isolated endothelium-denuded segments of the rabbit jugular vein where bradykinin elicits a constrictor response which is exclusively mediated by activation of the B2 receptor. 2. Moexiprilat and ramiprilat (< or = 3 nM) enhanced the constrictor response to bradykinin three to four fold. Captopril and enalaprilat were less active by approximately one and quinaprilat by two orders of magnitude. Moexiprilat and ramiprilat, on the other hand, had no effect on the constrictor response to AII or the dilator response to acetylcholine. 3. The bradykinin-potentiating effect of the ACE inhibitors was not mimicked by inhibitors of amino-, carboxy-, metallo- or serine peptidases or the synthetic ACE substrate, hippuryl-L-histidyl-L-leucine, at a concentration which almost abolished the residual ACE activity in the vessel wall. In contrast, angiotensin-(1-7) (10 microM), an angiotensin I metabolite, significantly enhanced the constrictor response to bradykinin. 4. Ramiprilat did not alter the binding of [3H]-bradykinin to a membrane fraction prepared from endothelium-denuded rabbit jugular veins or to cultured fibroblasts, and there was no ACE inhibitor-sensitive, bradykinin-induced cleavage of the B2 receptor in cultured endothelial cells. 5. These findings demonstrate that ACE inhibitors selectively potentiate the B2 receptor-mediated vascular effects of bradykinin. Their relative efficacy appears to be independent of their ACE-inhibiting properties and might be related to differences in molecule structure. Moreover, the potentiation of the biological activity of bradykinin by this class of compounds does not seem to be mediated by a shift in affinity of the B2 receptor or a prevention of its desensitization, but may involve an increase in the intrinsic activity of unoccupied B2 receptor molecules.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of barbiturates on the expression of the inducible nitric oxide synthase in vascular smooth muscle.

Certain cytokines stimulate the expression of the inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMCs) and in many other cell types. The large amounts of nitric oxide (NO) generated by iNOS in the vascular wall contribute to the unrelenting hypotension in septic shock. Because septic patients are often treated with barbiturates, we examined the effect of these anesthetic agents on the expression of iNOS in VSMCs. The induction of iNOS was elicited either in cultured rat aortic SMCs [interleukin-1beta (IL-1beta), 60 U/ml for 24 h] or in endothelium-denuded segments of the rabbit carotid artery [IL-1beta (100 U/ml) for 7 h]. The activity of iNOS was assessed by the accumulation of nitrite in the conditioned medium of cultured VSMCs and by the hyporeactivity of carotid arteries to phenylephrine. Moreover, iNOS protein abundance was determined by Western blot analysis, iNOS messenger RNA (mRNA) by reverse transcription followed by the polymerase chain reaction (PCR), and activation of the transcription factor NF-kappaB by gel electrophoretic mobility-shift analysis of nuclear extracts from VSMCs. The IL-1beta-stimulated increase in nitrite formation, iNOS protein, and mRNA abundance in VSMCs was significantly augmented in the presence of thiopental (100 microM), whereas methohexital, hexobarbital, pentobarbital, and phenobarbital were without effect. The potentiating effect of thiopental was observed only when the barbiturate was administered during the first 2 h of the 24-h incubation period of cultured VSMCs with IL-1beta. Thiopental did not affect the IL-1beta-stimulated activation of NF-kappaB in VSMCs. This barbiturate also significantly augmented the hyporeactivity to phenylephrine in carotid arteries exposed to IL-1beta, an effect that was abolished by N(G)-nitro-L-arginine. Exposure of either cultured or native VSMCs to thiopental alone did not stimulate iNOS expression. These findings demonstrate that the thiobarbiturate thiopental, but not oxybarbiturates, augments the IL-1beta-stimulated synthesis of NO in both cultured and native VSMCs. This effect of thiopental is the result of an increased expression of iNOS, involving most likely mechanisms distinct from NF-kappaB activation. The use of thiopental for long-term treatment of septic patients might possibly potentiate the biosynthesis of NO in the vascular wall and thus cause a further deterioration of the hemodynamic state.

Anesthetics, Intravenous↗
PubMed1997

Financing reforms in the German hospital sector: from full cost cover principle to prospective case fees.

OBJECTIVES: The authors provide an overview of the hospital sector in Germany with a focus on the impact of recent reform legislation on this sector. METHODS: Data from the Federal Statistics Office, the Ministry of Health, and the Federal Association of Physicians are synthesized with information obtained from a general review of the literature. RESULTS: Before the implementation of recent health-care reforms, the German health-care system has been sharply divided into inpatient and ambulatory care sectors, resulting in a fragmented system of care delivery. All hospital operating costs were fully covered through per diem charges. The 1992 Health Care Structure Act and subsequent pieces of legislation have introduced new mechanisms to improve cost efficiency in the hospital sector and increase coordination between the inpatient and outpatient care. These measures notably include implementing an inpatient prospective payment system and permitting ambulatory surgery and care services to be offered in inpatient settings. CONCLUSIONS: Whereas prospective payments have greatly reduced the length of stay, hospitals were reluctant to offer ambulatory surgery due to budgetary constraints and the high level of ambulatory surgery by office-based physicians. The reforms passed have not yielded substantial cost savings. These reforms offer a natural experiment that could benefit from national and international studies on the impact of hospital sector redesign on management, financing, and patient outcomes.

Financial Management, Hospital↗
PubMed1997

Hospital outcomes research in Germany: results from a retrospective survey among sickness fund beneficiaries.

OBJECTIVES: The authors assess the feasibility of using retrospective, indication-specific patient surveys to conduct hospital outcomes research in Germany. Surgical outcome and patient satisfaction were examined in patients who underwent common elective surgical procedures. METHODS: Using the International Classification of Diseases Ninth Revision coding available in the Schwäbisch Gmünd health insurance data base, all patients for a defined period of time with one of the three following diagnoses were selected and questioned retrospectively using an indication-specific survey instrument: (1) varicose veins of the lower extremity; (2) nasal septum deviation; and (3) inner knee joint damage limited to patients undergoing arthroscopic meniscus repair. Survey content focused on preoperative conditions, pre- and postoperative symptoms, postoperative complications, the nature and duration of postoperative follow-up, and satisfaction with surgical outcome. RESULTS: Significant postoperative improvement of preoperative symptoms was found for all three groups. Complete freedom from symptoms was found in 29.7% of patients treated for varicose veins, 24.1% of patients with meniscus repair, and in only 10.6% of patients with nasal septum deviation. Multivariate analyses indicated that postoperative impairment was the decisive variable governing patient satisfaction for all three groups. CONCLUSIONS: The use of retrospective, indication-specific patient surveys constitutes a time-efficient, cost-effective, and patient-focused option for the systematic acquisition and evaluation of health outcomes in Germany. This methodology holds promise for international and domestic efforts to demonstrate the consequences of restructuring activities in the inpatient sector.

Adult↗
PubMed1997

Regional measurements of NO formed in vivo during brain ischemia.

Nitric oxide formed in vivo in the rat brain regions of hippocampus, striatum, neocortex and cerebellum was spin trapped and measured ex vivo by cryogenic electron paramagnetic resonance spectroscopy. In non-ischemic control animals the rate of nitric oxide (NO) formation in the individual brain regions ranged from 15 to 42 pmol.g-1.min-1. During exposure to global ischemia for 7 min the generation of NO increased in all parts of the brain. In the hippocampus the rate of NO formation during ischemia increased by 6-fold from a control rate of 19 pmol.g-1.min-1. This increase was attenuated 47% by pretreatment with the NO synthase antagonist 7-nitroindazole, whereas pretreatment with the non-NMDA receptor anatogonist NBQX and the Ca2+ channel blocker NS638 did not influence the NO formation. The data show that short-duration ischemia elicits a significant, NO-synthase-dependent formation of NO in all brain regions.

Analysis of Variance↗
PubMed1997

Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity.

OBJECTIVES: To determine the feasibility of monitoring the serum concentration of NG-hydroxy-L-arginine (L-NHA) as an index of an increased nitric oxide (NO) synthase activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) compared with nitrate (NO3-), the major circulating metabolite of NO whose concentration is influenced by dietary intake. METHODS: The serum concentrations of L-NHA, L-arginine (L-Arg), and NO3- were determined in 33 patients with RA, 25 patients with SLE and, 29 healthy subjects. RESULTS: Serum L-NHA was significantly increased in RA patients with high disease activity (287% of control, p < 0.01), but not with low disease activity (115%), as well as in patients with SLE (173%, p < 0.01). In contrast, serum NO3- did not differ significantly between either group of patients and the respective control group. CONCLUSION: NO synthase activity or expression, or both, is upregulated in RA patients with high disease activity and in patients with SLE. Serum L-NHA seems to be a more specific and reliable index of an increased activity of this enzyme in patients with acute or chronic inflammatory diseases than NO3-.

Acute Disease↗
PubMed1997

N-alpha-tosyl-L-lysine chloromethylketone prevents expression of iNOS in vascular smooth muscle by blocking activation of NF-kappa B.

Certain cytokines and lipopolysaccharide stimulate expression of inducible nitric oxide synthase (iNOS) in vascular smooth muscle, an event that is regulated at the transcriptional level and appears to involve several transcription factors, including nuclear factor kappa B (NF-kappa B). Since proteases play an essential role in NF-kappa B activation, experiments were designed to clarify, in both cultured rat aortic smooth muscle cells (SMCs) and isolated rat aortas, whether protease inhibitors affect the interleukin-1 beta (IL-1 beta)-elicited expression of iNOS. The formation of NO was assessed by nitrite release in cultured SMCs and the attenuation of phenylephrine-induced contraction in aortic rings, the expression of iNOS by Western blot analysis and reverse transcription-polymerase chain reaction, and NF-kappa B activity in nuclear extracts by gel electrophoretic mobility shift assya. Exposure of cultured SMCs to IL-1 beta increased NF-kappa B binding activity within 30 minutes and was associated with nitrite accumulation and the appearance of iNOS protein 24 hours later. These responses were abolished in cells that had been exposed to the cytokine in the presence of the protease inhibitor N-alpha-tosyl-L-lysine chloromethylketone. Aprotinin and p-toluenesulfonyl-L-arginine methyl ester, two other protease inhibitors, also reduced the cytokine-stimulated release of nitrite and the level of iNOS protein. Exposure of rat aortic segments without endothelium to IL-1 beta activated NF-kappa B within 30 minutes and was associated with the appearance of iNOS mRNA and an attenuation of phenylephrine-induced contraction 6 hours later. These responses were blunted when the segments were incubated with the cytokine and N-alpha-tosyl-L-lysine chloromethyl ketone. The present observations indicate that protease inhibitors prevent iNOS expression in both cultured and native vascular SMCs by blocking the activation of NF-kappa B.

Animals↗
PubMed1997

Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels.

Endothelium-dependent relaxations mediated by nitric oxide (NO) are attenuated in arteries exposed to proinflammatory mediators. Because proinflammatory mediators stimulate the expression of the inducible NO synthase (iNOS) in vascular cells, the role of iNOS-derived NO in the impaired endothelium-dependent relaxation was examined in arterial ring preparations. Exposure of rabbit carotid arteries to interleukin-1 beta (IL-1 beta; 100 U/mL for 7 hours) and porcine coronary arteries to a combination of tumor necrosis factor-alpha (1000 U/mL), interferon-gamma (500 U/mL), and lipopolysaccharide (10 micrograms/mL) for 15 hours (conditions that are associated with iNOS expression) markedly attenuated relaxations to receptor-dependent agonists, whereas those to the calcium ionophore A23187 and sodium nitroprusside were virtually unchanged. The impaired relaxation was not associated with a reduced level of the constitutive endothelial NOS (cNOS) but was accompanied by a reduced formation of biologically active NO as assessed in a bioassay system. The attenuated relaxation of carotid arteries to acetylcholine was not affected by superoxide dismutase and was neither found in arteries exposed to IL-1 beta for only 15 minutes nor in IL-1 beta-treated arteries for 7 hours followed by a 17-hour incubation period without the cytokine. Furthermore, no impaired relaxation was found in rings exposed to IL-1 beta in combination with either cycloheximide or N-alpha-tosyl-L-lysine chloromethyl ketone or pyrrolidine dithiocarbamate, treatments that prevent iNOS expression. In addition, selective inhibition of iNOS with S-methylisothiourea (10 mumol/L) completely restored acetylcholine-induced relaxations. These findings indicate that the continuous generation of NO induced by proinflammatory mediators plays a major role in the inhibition of endothelium-dependent relaxation, most likely by impairing a step in the signal transduction cascade that links activation of endothelial receptors to the calcium-calmodulin-dependent activation of NOS.

Acetylcholine↗
PubMed1997

Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production.

We investigated the effects of aortic banding-induced hypertension on the endothelium-dependent vasodilator responses in the aorta and coronary circulation of Sprague-Dawley rats. We studied the influence of hypertension on the endothelial nitric oxide synthase (NOS III) expression, assessed by Western blot and reverse transcription-polymerase chain reactions experiments, and on the superoxide anion (O2-) production. Two weeks after aortic banding, the endothelium-dependent relaxations were not altered. At this time, the expression of NOS III in the aorta and in confluent coronary microvascular endothelial cells (RCMECs) exhibited no marked changes, whereas O2- production was enhanced 1.9-fold in aortas from aortic-banded rats. Six weeks after aortic banding, the endothelium-dependent dilations were markedly impaired in the heart (50% decrease) and aorta (35% decrease). Analysis of NOS III protein and mRNA levels revealed marked increases in both aortas and confluent RCMECs (2.6- to 4-fold) from aortic-banded compared with sham-operated rats. There was no further increase in O2production in both the aorta and confluent RCMECs from aortic-banded rats. An enhanced nitrotyrosine protein level was also detected in the aorta from 6-week aortic-banded rats. These findings indicate that in hypertension induced by aortic banding, an enhanced O2- production alone is not sufficient to produce endothelial dysfunction. Endothelial vasodilator hyporesponsiveness was observed only when NOS III expression and O2- production were increased and was associated with the appearance of enhanced nitrotyrosine residues. This would suggest that the development of endothelial dysfunction is linked to an overproduction of not one, but two, endothelium-derived radicals that might lead to the formation of peroxynitrite.

Animals↗
PubMed1997

Endothelium-derived hyperpolarizing factor, but not nitric oxide, is reversibly inhibited by brefeldin A.

The subcellular localization of the enzymes synthesizing endothelium-derived vasodilator autacoids has been proposed to play a role in determining the ability of endothelial cells to enhance autacoid production in response to stimulation. We therefore investigated the effects of brefeldin A-induced disruption of the Golgi apparatus and Golgi-plasma membrane trafficking on the production of nitric oxide (NO), prostacyclin, and the endothelium-derived hyperpolarizing factor (EDHF) by native and cultured endothelial cells. In porcine coronary artery segments, brefeldin A (35 micromol/L, 90 minutes) did not affect relaxations to sodium nitroprusside or the K+ channel opener cromakalim but elicited a rightward shift in the concentration-response curve to bradykinin without altering the maximum vasodilator response (Rmax). Brefeldin A failed to attenuate the bradykinin-induced, NO-mediated relaxation under depolarizing conditions but inhibited the bradykinin response under conditions of combined cyclooxygenase/NO synthase blockade, suggesting that this agent selectively interferes with the production of EDHF. Indeed, incubation of porcine coronary arteries with brefeldin A, which did not affect the bradykinin-induced accumulation of either cyclic GMP or 6-keto-prostaglandin F1alpha, markedly and reversibly attenuated the EDHF-mediated hyperpolarization of detector smooth muscle cells in a patch-clamp bioassay system. The microtubule destabilizer nocodazole also affected both the EC50 and Rmax to bradykinin in porcine coronary arteries. Since EDHF is thought to be a cytochrome P450-derived metabolite of arachidonic acid and both brefeldin A and nocodazole are known to interfere with the targeting of cytochrome P450 from the Golgi apparatus to the plasma membrane, it is conceivable that brefeldin A inhibits EDHF formation by preventing the targeting of the EDHF-synthesizing enzymes to the plasma membrane.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

[Observations on social medicine in public health transition].

In spite of the growing criticism of the social welfare principles, the social health insurance model is remarkably stable in Europe. Key features of this model are even implemented in more market oriented models (as in Switzerland) and in national health systems as in the United Kingdom. In Germany, however, the discussion is almost solely centred around the argument of globalisation of capital and labour and, subsequently, the high additional costs on labour. This endangers social security which is financed through wages. If the social welfare system in Germany would be abolished de facto and not intelligently adapted, this would be a dramatic signal against social principles all over Europe. Consequences for social medicine as a scientific discipline are: Social medicine as a public health discipline with the goal of equality in health care must get involved in health politics. Social medicine as an empirical science has to evaluate- and refute, if necessary-existing myths and prejudices. Social medicine needs a stable network for research, teaching and practice-this is the growing field of "public health".

Cost Control↗
PubMed1997

[General practice management and therapy of terminally ill patients--a longitudinal study].

Since most persons in Germany die outside a hospital, the aim of the study was to quantify GP and nursing services for persons in the ten weeks prior to death. GPs were asked to document patients they considered to be terminal, using a set of different documentation sheets: 1. age, sex, living situation, and diagnoses, 2. time, place, duration, services, and nursing intensity for every contact and 3. circumstances of death. GPs were told to expect three-month periods to be documented. Twenty-six practices participated, documenting 47 patients and 582 contacts. Mean age of the deceased was 76 years (31 to 98); 21 were male and 26 female. Patients were classified as "terminal" on average 70 days prior to death (median 50 days). Average number of doctor-patient contacts increased from 0.7/week to 1.6 in the third and second last week and 2.4 in the final week. Average number of hospital days were around 1.1/week for the whole period. Nursing hours by relatives increased to over 13 h/day in the final week. Professional home nursing services were available for 80% in the final week, but only for 3 h/day. Thirty-two patients (68%) died at home, 7 (15%) in a nursing home and 8 (17%) in hospital (after a mean of 6 days as in-patients). The results document the large amount of time needed by physicians, relatives and nurses in the last weeks of life for persons who die at home.

Adult↗
PubMed1997

[Social health insurance for all: can we learn from Japan?].

In the current German health care reform debate, the only foreign experiences discussed are from the USA or UK even though other countries have systems much more similar to that of Germany. Based on the German model of statutory health insurance. Japan has developed a similarly financed health system which has been quite successful in cost containment since the early 1980's. Unlike Germany, Japan has included the whole population in its statutory insurance scheme and refrains from private health insurance and upper limits on contributory income. Other features include the inclusion of pharmaceuticals in the Uniform Value Scale for all services, bi-annual revisions of that scale based upon utilization and technological innovation, government subsidies to health care which serve as a quasi global budget, and lastly a steadily growing GDP. Differences in the systems include the Japanese mixture of the ambulatory, in-patient and pharmaceutical sectors with physicians both in private practice and hospitals offering all three kinds of services. In-patient utilization is characterized by high numbers of hospital beds, very long lengths of stay, and few cases. Problems of the Japanese systems include the relatively low satisfaction of both population and patients, and the lack of quality assurance measures, clinical guidelines, and continuing education.

Cost Control↗
PubMed1997

[Evaluation of cost effectiveness in primary health care].

Evaluation of Cost-Effectiveness in Health Care considers the background, methodology and potential political influence of economic evaluation (EE) in health care, the following conclusions can be drawn: EE is not just about cost cutting--it considers both costs and outcomes. EE needs to be integrated with decision-making procedures at different levels, namely the macro (policy) level, the meso (management) level, and the micro (clinical) level. EE needs to be seen as a part of a broader effort in health technology assessment and in relation to parallel efforts, e.g. guidelines development, quality assurance, evidence-based medicine. EE needs to be methodologically sound, but is not always possible to undertake the perfect study due to constraints of resources, time, information availability. Ways of setting priorities for EE need to be developed; this means selecting relevant topics and researchable questions. EE needs to be locally relevant; this means taking into account the variations of setting--within and between countries--and differences between trials (efficacy) and regular practice (community effectiveness). Factors that either encourage or inhibit the adoption of study results, i.e. adequate dissemination, professional support, financial incentives or political will, have to be considered.

Cost-Benefit Analysis↗
PubMed1997

[Why do adults with mucoviscidosis refuse a medically recommended course of intravenous antibiotic therapy?].

BACKGROUND: Regular courses of intravenous antibiotics are recommended for the treatment of chronic Pseudomonas aeruglnosa (PA) infection in patients with cystic fibrosis. We report the results of interviews performed to evaluate why a subgroup of patients vote against regular intravenous (i.v.) antibiotic treatment. METHODS: Structured interviews covering a) the individual's perception of chronic PA infection, b) the patient's expectations regarding the effectiveness of i.v. treatment, c) the patient's personal reasons for refusal of i.v. treatment. STUDY COHORT: 16 out of 18 adult patients treated in the adult CF outpatient clinic at Hannover Medical School who had voted against the physician's recommendation to receive regular i.v. therapy twice a year. RESULTS: More than one half of the patients did not regard chronic PA infection as important due to the lack of specific symptoms. A subgroup of patients had no idea of what their clinical status should be if i.v. antibiotics would be necessary; these patients reported prior experience of treatment courses which had been ineffective and had been instituted after talking into the patients. The most frequent reasons against IV treatment were not being sick enough and fear of adverse drug effects. ASSESSMENT: The results are being discussed considering the physician-patient relationship. The reasons why patients refuse help should be extensively explored rather than simply addressing this attitude as "non-compliance". Patients, too, come to reasonable decisions, and it is important to know their thoughts and reasoning if one intends to influence them.

Adult↗
PubMed1996

A transferable, beta-naphthoflavone-inducible, hyperpolarizing factor is synthesized by native and cultured porcine coronary endothelial cells.

1. The vascular endothelium releases a hyperpolarizing factor (endothelium-derived hyperpolarizing factor, EDHF) tentatively identified as a cytochrome P450-derived arachidonic acid metabolite. However, there is still controversy concerning its transferability and identity. We designed a bioassay system for assessing EDHF release in which the membrane potential was recorded in cultured vascular smooth muscle cells located downstream from donor endothelial cells. 2. Under combined nitric oxide (NO) synthase and cyclo-oxygenase blockade with NG-nitro-L-arginine (100 mumol l-1) and diclofenac (10 mumol l-1), the superfusate from bradykinin (30 mumol l-1)-stimulated, cultured porcine coronary endothelial cells induced a distinct hyperpolarization followed by a depolarization. Direct application of bradykinin to the smooth muscle cells resulted solely in membrane depolarization. Similar results were obtained using bradykinin-stimulated porcine coronary arteries as donor. 3. Single-channel current measurements suggest that this EDHF-induced hyperpolarization was elicited by the activation of Ca(2+)-dependent K+ channels. 4. Increasing the transmural pressure within the donor segment significantly enhanced the duration, but not the amplitude of the hyperpolarization induced by the effluate from bradykinin-stimulated donor segments. 5. Inhibition of P450 oxygenase activity with clotrimazole (3 mumol l-1) or 17-octadecynoic acid (3 mumol l-1) abolished EDHF release from the coronary endothelium, while the P450-derived arachidonic acid metabolite, 5,6-epoxyeicosatrienoic acid, induced a hyperpolarization of detector smooth muscle cells almost identical to that induced by EDHF. Moreover, induction of P450 activity by beta-naphthoflavone (3 mumol l-1, 48 h), significantly increased the bradykinin-induced release of EDHF. 6. These findings suggest that the vascular endothelium releases a transferable hyperpolarizing factor, chemically distinct from NO and prostacyclin, in response to agonists and mechanical stimulation. This beta-naphthoflavone-inducible EDHF appears to be a cytochrome P450-derived metabolite of arachidonic acid, which elicits hyperpolarization by activation of Ca(2+)-dependent K+ channels.

8,11,14-Eicosatrienoic Acid↗