[Spiritual needs of patients in an emergency room]. / Spirituelle Bedürfnisse von Patienten eines Notfallzentrums.

BACKGROUND: Spiritual needs (spN) are important for human beings-independently of religious affiliation. They can be a resource for coping with stressful situations, e.g., those triggered by the acute onset of a disease. Emergency rooms are hospital departments with high medical performance which may cause a particular insecurity among emergency patients. The present study is the first to examine spiritual needs in a sample of patients in the emergency room. METHODS: A total of 383 out of 479 patients were approached and asked to complete the German version of the Spiritual Needs Questionnaire (SpNQ-20). All consented to the collection of demographics and clinical data. The analysis encompassed descriptive statistics, correlations analysis, univariate and multiple variance analysis. RESULTS: The needs for inner peace and generative needs (to pass something on to others, to do something for others) were more important than religious (rN) and existential (eN) needs. We did not find a correlation between spN on the one hand and the reason for consultation, the severity, and the number of comorbidities on the other hand. Age did not play a decisive role, rather, patients' needs, especially rN, were significantly more important among women than among men. CONCLUSION: Even in an emergency situation, people are ready to express their spN. Early assessment of these needs exposes important nonmedical aspects of the sick person and helps to consider the assessed needs. Further studies will show whether this has an impact on the further course of treatment and the well-being of the patients.

[Incidence of psychic comorbidity in inpatient pneumological rehabilitation and indication for psychological counselling/psychotherapy]. / Häufigkeit psychischer Komorbiditäten in der stationären pneumologischen Rehabilitation und Indikationsstellung zu psychol. Beratung/Psychotherapie.

The present study examines psychic comorbidities in patients with chronic diseases of the airways in pneumological rehabilitation centres and the indication for psychological counselling/psychotherapy. It is thus intended to help provide a rational basis for psychological and psychotherapeutic help in inpatient pneumological rehabilitation. According to accepted psychiatric screening scales (BSI, HADS), 30 % of the 159 examined patients undergoing rehabilitation were conspicuous in both questionnaires (BSI and HADS-D) and further 51 % were considered as conspicuous in one of the questionnaires. About 3 % of the pneumological patients in the Allgäu centre had a medical indication for psychological counselling/psychotherapy. In this respect the indication proved to be valid. The group of patients who were not referred to a psychological counselling/psychotherapy in spite of an existing psychic impairment showed a significantly lower motivation for treatment and a lower psychic tolerance. The large proportion of psychic stress confirms the relevance of psychological and/or psychotherapeutic help in pneumological rehabilitation.

Impact of medical and demographic factors on long-term quality of life and body image of breast cancer patients.

BACKGROUND: The impact of various medical and demographic factors on the quality of life (QoL) of breast cancer patients has been discussed controversially. We investigated the influence of six different factors on long-term QoL and body image of women with primary breast cancer. PATIENTS AND METHODS: Two-hundred and seventy-four breast cancer patients were administered the QoL questionnaire following a mean interval of 4.2 years after primary diagnosis. All women had been primarily treated for stage I to III breast cancer without evidence of distant metastases. QoL was evaluated by using the QLQ-C30 questionnaire Version 2.0. Supplementary scales included body image, satisfaction with surgical treatment, cosmetic result and fear of recurrence. We analyzed the impact of tumor stage, surgical treatment, adjuvant radiotherapy, adjuvant cytotoxic therapy, age and length of follow-up period on the examined outcome parameters. RESULTS: At the time of the follow-up examination, patients showed minor impairment of QoL (mean 67.8) and body image (mean 24.8), but more fear of recurrence (mean 60.7). None of the studied factors had a significant impact on overall QoL (P >0.05) according to the QLQ-C30 questionnaire. In contrast, with the exception of the factors 'cytotoxic therapy' and 'radiotherapy' all investigated variables influenced at least one of the additional psychological scales (P <0.05). The primary surgical treatment modality had the strongest impact and affected all four scales. Patients treated with breast conservation reported a more favorable body image, compared to those treated with mastectomy (17.2 versus 37.5, P <0.01), more satisfaction with surgical treatment (4.0 versus 10.7, P = 0.01), rated a better cosmetic result (75.5 versus 57.1, P <0.01), but presented more fear of recurrence (63.9 versus 55.3, P = 0.04). CONCLUSION: Current QoL questionnaires do not sufficiently cover all relevant aspects of QoL, but might be complemented by breast cancer specific aspects such as body image and fear.

[Specific concepts of care for pregnant women with drug addiction or HIV infection]. / Spezifische Betreuungskonzepte für schwangere Frauen mit Sucht- bzw. HIV-Konflikten.

In the last 10 years about 130 women with a drug addiction and more than 100 HIV-positive pregnant women were treated at the 1. University Hospital of Obstetrics and Gynaecology in Munich. Besides a specialized medical treatment both groups required intensive psychosocial care. HIV-infected people are still isolated and suffer from the social stigmata. Their essential needs for sexuality and children of their own are often ignored or even condemned because of irrational fears about HIV, which continue despite rapid medical improvements. The life-expectancy for example has increased since the inauguration of protease inhibitors. Vertical transmission of HIV is below 2% through medical treatment in pregnancy, elective cesarean section and renunciation of breastfeeding. Drug addicted pregnant women are given the opportunity to change their life in order to care for their children appropriately. The basis for this is a substitution with levomethadone and elimination of the use of other drugs. The addicted women often can reduce the dosage of levomethadone during the course of their pregnancy and sometimes can cease totally. Normally they are highly motivated and thus can ease the withdrawal symptoms of their newborns following delivery. By establishing a reliable social net during pregnancy mothers learn to recognize the demands of their children after birth and thus emotional and cognitive deficits can be prevented.

Development of potent thrombin receptor antagonist peptides.

A peptide-based structure-activity study is reported leading to the discovery of novel potent thrombin receptor antagonists. Systematic substitution of nonproteogenic amino acids for the second and third residues of the human thrombin receptor "tethered ligand" sequence (SFLLR) led to a series of agonists with enhanced potency. The most potent pentapeptide agonist identified was Ser-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-NH2, 9 (EC50 approximately 0.04 microM for stimulation of human platelet aggregation, approximately 10-fold more potent than the natural pentapeptide). Systematic substitution of the NH2-terminal Ser in 9 with neutral hydrophobic NH2-acyl groups led to partial agonists and eventually antagonists with unprecedented potency (greater than 1000-fold increase over the previously reported antagonist 3-mercaptopropionyl-Phe-Cha-Cha-Arg-Lys-Pro-Asn-Asp-Lys-NH2). In the series of NH2-acyl tetrapeptide antagonists, N-transcinnamoyl-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-NH 2, 41 (BMS-197525), was identified as the tightest binding (IC50 approximately 8 nM) and most potent with an IC50 approximately 0.20 microM for inhibition of SFLLRNP-NH2-stimulated platelet aggregation. Systematic single substitutions in 41 indicated that, in addition to the NH2-terminal acyl group, the side chains at the second and third positions were also responsible for important and specific receptor interactions. The p-fluoroPhe and p-guanidinoPhe residues in the second and third positions of 41 were observed to be optimal in both the agonist and antagonist series. In the case of antagonists, however, an appropriately positioned positively charged group (i.e., protonated base) at the third residue was required. In contrast, such a substitution was not required for potent agonist activity. An even more potent antagonist resulted when 41 was extended at the C-terminus by a single Arg residue giving rise to analog 90 (BMS-200261) which had an IC50 approximately 20 nM for inhibition of SFLLRNP-NH2-stimulated platelet aggregation. When the C-terminal Arg of 90 was replaced by an Orn-(Ndelta-propionyl) residue, the resulting antagonist 91 (BMS-200661) was suitable for use in radioligand binding assays (Kd = 10-30 nM). Antagonist activity observed for selected compounds was verified through secondary assays in that these analogs prevented SFLLRNP-NH2-stimulated GTPase activity in platelet membranes and Ca2+ mobilization in cultured human smooth muscle cells and mouse fibroblasts. Furthermore, this inhibition occurred at concentrations that had no effect on thrombin catalytic activity indicating a specific activity attributable to receptor binding and not enzyme inhibition.

Non-prostanoid prostacyclin mimetics. 6. Derivatives of 2-[3-[2-(4,5-Diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid modified beta-to the oxazole ring.

2-[3-[2-(4,5-Diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid, 1, has been described as a non-prostanoid PGI2 mimetic that demonstrates anti-thrombotic properties of long duration in animal models of thrombosis. The effects of substitution and modification of the carbon beta-to the oxazole heterocycle of 1 were examined and equated with the potency of the compounds as inhibitors of ADP-induced human platelet aggregation in vitro. Potency was sensitive to both the size of the substituent and the identity of the beta-atom. The carbamates 13c-e demonstrated IC50's of 0.28-0.36 microM and were significantly more potent than the progenitor 1, IC50 = 1.2 microM. The ethyl carbamate 13c displaced [3H]-iloprost from platelet membranes in a concentration-dependent fashion that was half maximal at 20 nM, which compares with IC50's of 171 nM for 1 and 39 nM or unlabelled iloprost. Carbamate 13c stimulated platelet adenylate cyclase but the maximal effect was less than that observed for PGI2, identifying 13c as a partial agonist at the platelet PGI2 receptor.

Nonprostanoid prostacyclin mimetics. 4. Derivatives of 2-[3-[2-(4,5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid substituted alpha to the oxazole ring.

The 4,5-diphenyloxazole derivatives 2-4 were previously identified as nonprostanoid prostacyclin (PGI2) mimetics. A series of derivatives of 2-4 bearing substitutents at the carbon atom alpha to the oxazole ring were synthesized and evaluated as inhibitors of ADP-induced aggregation of human platelets in vitro. In the unsaturated series, the alpha-carbethoxy derivative 10a, evaluated as an equal mixture of geometrical isomers, inhibited platelet aggregation with an IC50 of 0.36 microM. Evaluation of the individual methyl ester derivatives (E)-9a and (Z)-9a revealed that (E)-9a was 10-fold more potent than (Z)-9a. In the saturated series, the alpha-carbomethoxy-substituted compound 12a inhibited platelet aggregation with an IC50 of 0.08 microM, 15-fold more potent than the unsubstituted prototype 2. The potency of 12a was found to be sensitive to variation of the methoxy moiety. The ethyl (12b) and isopropyl (12d) esters were less effective as were the acid 12e and a series of amides (12f-h). Other substituents introduced at this site of the pharmacophore included P(O)(OEt)2 (25), SCH3 (31a), S(O)CH3 (31b), SO2CH3 (31c), isopropyl (31d), phenyl (31f), and CH2OH (31i). However, none were significantly more potent inhibitors of platelet function than the parent compound 2. The results indicate the presence of a pocket in the PGI2 receptor protein that preferentially recognizes small, polar but uncharged substituents. The structure-activity correlates are suggestive of a hydrogen-bond interaction between a donor moiety on the PGI2 receptor and the methoxycarbonyl functionality of 12a that is sensitive to both the size of the substituent and its stereochemical presentation in this structural class of PGI2 mimetic. The ethyl ester 12b dose-dependently displaced [3H]iloprost from human platelet membranes and stimulated adenylate cyclase. However, the maximal stimulation was less than that recorded for iloprost, indicating that 12b functions as a partial agonist at the PGI2 receptor.

Isolation and identification of lysophosphatidylcholines as endogenous modulators of thromboxane receptors.

Inhibition of thromboxane receptor radioligand binding to human platelet membranes has been employed as the basis for a radioreceptor assay designed to measure thromboxane receptor binding activity in samples of biological fluids. This method was used during phase 1 clinical evaluation of the thromboxane receptor antagonist SQ 30,741. Frequently, baseline plasma samples as well as plasma samples from placebo-treated subjects showed significant inhibition of radioligand binding in the radioreceptor assay, suggesting the presence of endogenous thromboxane receptor ligands. This receptor binding activity was stable and could be monitored in blood from normal volunteers using a modification of the radioreceptor assay. In order to identify the substance responsible for the observed activity, the activity present in pooled bovine blood was isolated and evaluated by a combination of FAB/MS, 1H-NMR, 13C-NMR and co-injection with reference standards on HPLC. Several endogenous thromboxane receptor ligands were identified as L-alpha-lysophosphatidylcholine (LPC) species. One major species, palmitoyl-LPC, contracted isolated rat aortic spirals, and these contractions could be delayed or prevented, but not reversed by the thromboxane receptor antagonist SQ 29,548. Palmitoyl-LPC slightly potentiated aortic contractions induced by the thromboxane receptor agonist, U-46,619, and diminished in a concentration-dependent manner the antagonism by SQ 29,548 of contractile responses to U-46,619. These findings are consistent with a potential for LPC species to bind and activate thromboxane receptors.

Prostacyclin agonists reduce early atherosclerosis in hyperlipidemic hamsters. Octimibate and BMY 42393 suppress monocyte chemotaxis, macrophage cholesteryl ester accumulation, scavenger receptor activity, and tumor necrosis factor production.

We determined the effects of two prostacyclin agonists (octimibate and BMY 42393) on the progression of the fatty streak in vivo and on macrophage function in vitro. Hamsters were fed chow plus 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with animals receiving either octimibate (10 or 30 mg/kg per day) or BMY 42393 (30 mg/kg per day). After 10 weeks of treatment, octimibate decreased plasma total cholesterol and triglycerides by 43% and 32%, respectively. Neither agonist affected blood pressure or heart rate. Lesion-prone aortic arches were stained with hematoxylin and oil red O and examined en face. Compared with controls, octimibate and BMY 42393 on average decreased mononuclear cells attached to the luminal surface by 44% and reduced subendothelial macrophage-foam cell number by 56%, foam cell size by 38%, and fatty streak area by 63%. Since octimibate is a putative inhibitor of acyl coenzyme A cholesterol acyltransferase, we studied the effect of both agents on cholesteryl ester metabolism in murine macrophages. At 10 microM, octimibate and BMY 42393 decreased cholesteryl ester accumulation in macrophages by 90% and 41%, respectively. Octimibate inhibited cholesteryl ester synthesis by 96% and increased the rate of cholesteryl ester degradation by 52%. Both prostacyclin agonists reduced macrophage scavenger receptor-mediated uptake of acetylated low density lipoprotein by 24-66% and increased cyclic adenosine monophosphate levels. Octimibate and BMY 42393 inhibited the secretion of tumor necrosis factor by 80-88% when macrophages were activated with lipopolysaccharide. At 10 microM, both agents decreased human monocyte chemotaxis to N-formyl-methionyl-leucyl-phenylalanine by 64-79%. The in vitro results with octimibate and BMY 42393 are consistent with the low number of small foam cells quantified in vivo. We suggest that octimibate and BMY 42393 suppress monocyte-macrophage atherogenic activity and cytokine production and thus inhibit the development of early atherosclerosis.

Pharmacological characterization of potent, long-acting thromboxane receptor antagonists, SQ 33,261 and SQ 33,552.

SQ 33,261 ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-6-[3-[[2- [(phenylamino)carbonyl]hydrazono]methyl]-7-oxabicyclo[2.2.1]hept-2 - yl]-4-hexenoic acid) and SQ 33,552 ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-6-[3-[[[[(4- chlorophenyl)amino]carbonyl]hydrazono]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]-4-hexenoic acid) are potent thromboxane (Tx) A2 receptor antagonists. They inhibited platelet aggregation in platelet-rich plasma induced by the TxA2 mimetic, U-46,619 (10 microM), with IC50 values of 200 and 70 nM, respectively. Neither compound inhibited ADP (20 microM)-induced platelet aggregation (IC50 greater than 1000 microM). SQ 33,261 and SQ 33,552 competitively antagonized U-46,619-induced contraction of rat aortic strips with respective pA2 values of 9.0 and 10.1 and KB values of 1.2 and 0.1 nM. They also competitively antagonized U-46,619-induced contraction of guinea pig tracheal strips with pA2 values of 8.9 and 9.9 and KB values of 1.9 and 0.4 nM, respectively. SQ 33,261 and SQ 33,552 (p.o.) were potent inhibitors of U-46,619 (2 mg/kg i.v.)-induced death in mice with ID50 values of 8 and 1 micrograms/kg, respectively. SQ 33,261 and SQ 33,552 (0.2 mg/kg p.o.), also had long duration of action in this assay with 50% survival times of 7 and 15 hr, respectively. SQ 33,261 at 0.01 and 1.0 mg/kg i.v., inhibited arachidonic acid-induced bronchoconstriction and reversed arachidonic acid-induced hypertension to a hypotensive response. SQ 33,552 inhibited TxA2 synthase at high concentrations (IC50 = 307 microM), whereas SQ 33,261 was inactive. Neither compound inhibited cyclooxygenase or caused an elevation of platelet cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A-way express: a way to empowerment through competitive employment.

As traditional vocational rehabilitation programs for the psychiatrically disabled have failed to improve participation of this most marginalized group in the labour force, alternatives are needed to deal with extremely high unemployment of psychiatric survivors. The following article describes a grassroots initiative that has considerably changed life and employment prospects of 50 consumers-survivors in Toronto.

Thromboxane receptor blockade prevents pulmonary hypertension induced by heparin-protamine reactions in awake sheep.

We used competitive thromboxane A2-prostaglandin endoperoxide receptor blockade (SQ 30,741) as a probe to evaluate the role of thromboxane in ovine pulmonary vasoconstriction associated with protamine reversal of heparin anticoagulation. Control heparin-protamine reactions induced rapid release of thromboxane into arterial plasma (more than 1 ng/ml plasma), a 2.5-fold increase of pulmonary artery pressure, a 20% decrease of PaO2, and a 30% reduction in arterial white blood cell concentration. After giving SQ 30,741 despite similar thromboxane release into arterial plasma after heparin-protamine challenge, acute pulmonary hypertension was significantly reduced when 94% of pulmonary vascular smooth muscle thromboxane receptors were occupied with SQ 30,741 (p less than 0.01 at 1 minute after protamine versus control heparin-protamine reaction) and was completely abolished by a 10 mg/kg i.v. bolus (p less than 0.0001 at 1 minute after protamine versus control). Peripheral leukopenia was not affected by SQ 30,741 prophylaxis, but hypoxemia was prevented. We conclude that thromboxane causes pulmonary vasoconstriction in ovine heparin-protamine-induced pulmonary hypertension. Pulmonary vasoconstriction and hypoxemia can be completely prevented by thromboxane receptor blockade.

Activity of the short-acting thromboxane receptor antagonist, SQ 30,741, in thrombolytic and vasospastic models in monkeys.

The effects of the thromboxane receptor antagonist SQ 30,741 (1 mg/kg) on reflow after thrombolysis and on vasoconstrictor responses to the thromboxane agonist U-46,619 was determined in cynomolgus monkeys. SQ 30,741 (n = 5) or vehicle (n = 4) was administered to anesthetized monkeys upon reocclusion of a stenotic and electrically injured carotid artery, which had been recanalized successfully with streptokinase and heparin. Once blood flow again decreased to zero the treatment was repeated. SQ 30,741 significantly (P less than .05) enhanced reflow by 113% after the first administration and by 150% after the second administration. The respective times to each reocclusion were greater after SQ30,741 (49 +/- 9 and 61 +/- 23 min; P less than .01 and P less than .05) than with vehicle (10 +/- 3 and 15 +/- 2 min). The potency of SQ 30,741 was demonstrated in other anesthetized monkeys by a 8.5 +/- 1.1-fold (n = 3) shift to the right in the U-46,619 dose-response for renal vasoconstriction. The effect of SQ 30,741 (n = 5) on pre-existing renal vasoconstriction was determined using conscious monkeys in which an individually tailored dose of U-46,619 was chosen to sustain an average 82% reduction in blood flow. An arterial injection of SQ 30,741 rapidly returned flow to base-line values, but this antagonism was limited in duration, and flow again reached the nadir within 46 +/- 7 min of continuous U-46,619 infusion. The abbreviated duration of the biological activity of SQ 30,741 in vivo was consistent with its short plasma T1/2 (9.5 +/- 1.3 min; n = 3) determined in separate unanesthetized monkeys by a radioreceptor assay.(ABSTRACT TRUNCATED AT 250 WORDS)