Organ transplantation in Greece: the need for mediation.

Organ transplants are not regarded as an exclusively medical process, because they involve financial, religious, philosophic, and bioethical parameters. It becomes clear that if they are to achieve their purpose, which we believe extends well beyond the medical dimension, the creation of a comprehensive framework of communication between the involved parties is of paramount importance. The aim of this paper is to present an outline and a number of considerations regarding the communicational, bioethical, and legal issues that arise from a rather dramatic state of affairs in Greece today: In 2012 the rate of organ transplants stood at only 7 per 1 million of the population. The outdated legal framework and the lack of trust on the part of patients and the public have led to a highly inefficient system that is lagging behind in many respects. The proposition made in this paper is that there is a need for a new system of communication between doctors, patients, relatives of patients, and hospitals: bioethical mediation. This is a system that has played a vital role and has produced astounding results in other countries. There is also every indication that the introduction of such a system is crucial for Greece, especially as the symptoms of the acute financial crisis are become fully visible and tangible. Mediation aims to identify solutions that are oriented toward the interests and wishes of patients, are acknowledged and accepted by all parties involved, and are in tune with the values and the principles of medical practice.

Minimally invasive vaginal hysterectomy using bipolar vessel sealing: preliminary experience with 500 cases.

The objective of our study was to evaluate surgical outcome of minimally invasive vaginal hysterectomy (MIVH), using the bipolar vessel sealing system (BVSS; BiClamp®). The design was a retrospective analysis (Canadian Task-force Classification II-3). The setting was a secondary care hospital. Records of patients who underwent vaginal hysterectomy for benign indications in our centre between November 2005 and March 2011 were reviewed. The demographic patients' data, indications for surgery, patient history with regard to previous surgery, duration of surgery, blood loss (postoperative hemoglobin drop '∆Hb'), perioperative complications, and length of inpatient stay were collected from the medical records. The intervention was vaginal hysterectomy using BVSS (BiClamp®). Results showed that the mean duration of surgery was 48.9 ± 15.3 min (95% CI, 49.2-52.5). The mean duration of hospital stay was 3.2 ± 1.2 days (95% CI, 2.8-3.2). The mean ∆Hb was 1.4 ± 1.8 g/dl. Overall, conversion to laparotomy was required in three cases (0.6%). Only one haemoperitoneum occurred (0.2%) and this is the only case who required blood transfusion. The main indication for VH was uterine prolapse in 52.0% (n = 260) of cases; uterine fibroids in 37.4% (n = 187); adenomyosis uteri in 4.2% (n = 21); cervical dysplasia in 22 patients (4.4%) and in 2% (n = 10) of patients, endometrial hyperplasia and other pathologies were the indications for VH. It was concluded that electrosurgical bipolar vessel sealing by (BiClamp®) can provide a safe and feasible alternative to sutures in vaginal hysterectomy, resulting in reduced operative time and blood loss, with acceptable surgical outcomes.

Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement.

OBJECTIVE: In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement. DESIGN: Prior to and after 2 months of transdermal oestradiol (50 microg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion. PATIENTS: Fourteen healthy postmenopausal women. MEASUREMENTS: Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test). RESULTS: Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0. 457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day. CONCLUSIONS: Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.

Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women.

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 micrograms/day of 17 beta-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection. Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 +/- 21.6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.

Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.

OBJECTIVE: Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli. METHODS: Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol. RESULTS: Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol. CONCLUSIONS: Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women.

The effect of a 2-mo treatment with transdermal estradiol (50 microgram/day) versus placebo on 24 h of blood pressure rhythm was investigated in 18 normotensive healthy postmenopausal women. Whereas daytime blood pressure was not modified, nighttime blood pressure was reduced by estradiol. Estradiol magnified the nocturnal decrement of systolic (14.3 +/- 7.2 vs. 9.8 +/- 6.7 mmHg, P = 0. 0033), diastolic (11.6 +/- 5.0 vs. 7.5 +/- 7.3 mmHg, P = 0.028), and mean (10.8 +/- 5.6 vs. 7.2 +/- 4.5 mmHg, P = 0.011) blood pressure. As a consequence, the 24-h rhythm of mean blood pressure was restored in 50% of the subjects (P = 0.045) in whom it was absent and was amplified in the remaining 50% of the subjects. Body mass index was an independent determinant of blood pressure values being directly related to the amplitude of the 24-h mean blood pressure rhythm (r2 = 0.38; P = 0.0067). In normotensive postmenopausal women, physiological doses of estradiol amplify the nocturnal decline of blood pressure.

Oral contraceptives and bone metabolism.

In women, the bone metabolism is markedly influenced by gonadal steroids and by their fluctuations. Indeed, estrogens influence bone metabolism by influencing endocrine and paracrine functions involved in bone remodelling. In normally cycling women, the administration of oral contraceptives does not increase bone mineral density and does not induce deleterious effects on bone. In women with ovulatory disturbances, bone turnover is increased and bone mineral density is lower than in normally cycling women. In these cases, administration of oral contraceptives is capable of blocking increased bone loss and of restoring a normal bone mineral density. Similarly, in women treated with gonadotropin releasing hormone (GnRH) analogs, the concomitant administration of oral contraceptives completely antagonizes GnRH analog-induced bone loss. The progestogenic component of oral contraceptives seems to contribute to the protective effect of estrogens on bone. Oral contraceptives are safe for bone maintenance in normal adult women, and are indeed indicated to prevent postmenopausal osteoporosis in women with ovulatory disturbances.

Anestesia barbitúrica de longa duraçäo em cäes com o emprego de tiopental, clorpromazina e diazepam / Long-term anesthesia in dogs with thiopental sodium, chlorpromazine and diazepan

O objetivo deste trabalho foi produzir anestesia barbitúrica de longa duraçäo, com emprego de tiopental, sem realizaçöes constantes da droga. Foram empregados 70 cäes, sem raça definida, adultos, de ambos os sexos e com pesos entre 8 e 12 kg. A cada animal foi administrado, por via intravenosa, 25 mg/kg de tiopental. Decorridos 10 minutos, foi aplicado, pela mesma via, 1 mg/kg de clorpromazina. Aguardaram-se 10 minutos e aplicou-se diazepam, na dose de 1 mg/kg, também por via intravenosa. Todos os animais foram submetidos à procedimentos cirúrgicos diversos e mensuraram-se as frequências cardíaca e respiratória e a temperatura retal, a intervalos de 10 minutos, durante 160 minutos. Pôde-se observar anestesia cirúrgica por 120 a 250 minutos. Näo se observaram variaçöes significativas nos resultados, à exceçäo de temperatura retal, que decresceu significativamente. Face ao extenso período de recuperaçäo, concluiu-se que a técnica é inadequada para uso na rotina clínica cirúrgica

Epitope mapping of the anti-urokinase monoclonal antibody 5B4 by isolated domains of urokinase.

The amino terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) is a degradation product comprising the entire growth factor-like and kringle domains. It has been previously shown that ATF is able to bind to the u-PA receptor through the growth factor-like domain and that the anti u-PA monoclonal antibody 5B4 (Mab 5B4) binds to ATF preventing u-PA receptor binding. To localize more precisely the epitope recognized by Mab 5B4, ATF was subfragmented by controlled enzymatic proteolysis with V8 protease. Three subfragments of 4,000 Mr (F-4k), 11,000 Mr (F-11k) and 12,000 Mr (F-12k) were purified from the reaction mixture and characterized. SDS-PAGE under reducing and non-reducing conditions, N-terminal aminoacid sequence analysis and C-terminal aminoacid analysis of each fragment indicate that F-4k and F-11k correspond to intact growth factor-like domain and kringle domain (residues 4-43 and 44-135 respectively) while F-12k corresponds to the kringle domain cleaved in the first loop at the glu52-gly53 bond. By Western blot and competitive binding experiments we show that Mab 5B4 recognizes an epitope located on the kringle domain of u-PA and that the binding is strongly reduced when the kringle contains an additional cleavage in its first loop. Since the receptor binding site of u-PA has been previously shown to be located on the growth factor-like domain, Mab 5B4 inhibits the binding of uPA to its cellular receptor likely by steric hindrance. Besides the proven utility in epitope localization of anti u-PA monoclonal antibodies, these u-PA fragments may represent powerful tools for studies of structure-function relationship of u-PA.

A double-blind controlled study to compare the efficacy of an antacid plus oxethazaine with that of an antacid alone in the treatment of pain due to gastric or duodenal ulceration.

A double-blind study was carried out in 40 patients with typical ulcer pain and suffering from gastric or duodenal ulcer to compare the pain-relieving efficacy of oxethazaine/magnesium and aluminium hydroxide mixture with that of the antacid combination alone. Patients took 8 ml doses of either treatment when necessary over a period of 4 weeks. Both treatment regimens were equally effective in reducing the painful symptoms of peptic ulceration, but the total volume of medication required to achieve adequate symptomatic relief was less in patients taking antacid plus oxethazaine than in patients taking antacid alone. It is suggested that the combination of oxethazaine plus antacids, therefore, is to be preferred, because, by allowing a reduction in the intake of antacid, the risk of side-effects due to antacid therapy is thereby reduced.