Pulmonary vein anatomy variants as a biomarker of atrial fibrillation - CT angiography evaluation.

BACKGROUND: It has been suggested that changes in pulmonary veins (PV) and left atrium (LA) anatomy may have an influence on initiating atrial fibrillation (AF) and the effectiveness of pulmonary vein isolation (PVI) in patients (pts) with atrial fibrillation. The aim of the study was to assess anatomy abnormalities of the PV and LA in the patients with the history of AF and compare it with the control group(CG). METHODS: The multi-slice tomography (MSCT) scans were performed in 224 AF pts. before PVI (129 males, mean age 59 ± 9 yrs). The CG consisted of 40 pts. without AF (26 males, age 45 ± 9 yrs). LA and PV anatomy were evaluated. Diameters of PV ostia were measured in two directions: anterior-posterior (AP) and superior-inferior (SI) automatically using Vitrea 4.0. RESULTS: Pulmonary veins anatomy variants were observed more frequently in the atrial fibrillation group - 83 pts. (37%) vs 6 pts. (15%) in CG; 9% (21 pts) left common ostia (CO), 2% (5 pts) right CO, 19% (42 pts) additional right PV (APV), (1.8%) 4 pts. APV left, 8% right early branching (EB) and 3.5% left EB. The LA diameter differed significantly in AF vs CG group (41.2 ± 6 mm vs 35 ± 4.2 mm, p < 0.0001) respectively. CONCLUSIONS: The anomalies of pulmonary vein anatomy occurred more often in pts. with AF. They can be defined as an image biomarkers of atrial fibrillation. Right additional (middle) pulmonary vein was the most important anomaly detected in AF patients as well as enlargered diameters of the LA and PV ostia.

[Religious and cultural aspects of organ transplantation]. / Aspects religieux et culturels liés à la transplantation d'organes.

The number of transplantations is mainly limited by the shortage of organs, thereby leading to potentially lethal delays for patients registered on waiting lists. Among the causes of refusals of organ donation, religious reasons are often advocated. In order to make the point, we organized a debate between representatives of secularism ( " laïcité ") and of the most represented religions in Belgium, i.e. catholic, Islamic and Judaic. Even though the representation of death was variable, organ donation is authorized and even encouraged by the fundamental texts. Refusals of organ donation result more often from personal interpretations by local preachers. Therefore, the gathering of political and religious authorities in order to promote organ donation is desirable instead of sowing doubt for pseudo-religious reasons.

En médecine de transplantation, la pénurie d'organes représente le principal obstacle et cause de retard aux greffes vitales pour les receveurs inscrits sur liste d'attente. Parmi les causes de refus de don d'organes, des raisons d'ordre religieux sont souvent invoquées. Afin de faire le point sur cette problématique, nous avons organisé un débat rassemblant des représentants de la laïcité et des religions monothéistes les plus représentées en Belgique : catholicisme, islam, judaïsme. Il est apparu que, si la représentation de la mort varie selon les courants, le don d'organes est en fait autorisé, voire encouragé par les textes fondateurs des trois religions. Les refus sont plutôt le fait d'une interprétation personnelle par des prédicateurs. Dès lors, il serait judicieux de rassembler les forces politiques et spirituelles afin de promouvoir le don d'organes plutôt que de semer le doute à son sujet sous des prétextes pseudo-religieux.

Genetic diversity of urinary bladder cancer and the risk of recurrence based on mutation analysis.

The aim of the study was to assess the genetic diversity of bladder cancer and determine the suitability of a proposed molecular marker panel to monitor the course of bladder cancer patients. The study involved 185 patients with diagnosed bladder cancer. The genetic diversity of the bladder cancer was evaluated by the prevalence of mutations in the TP53, HRAS, FGFR3 and WWOX genes. Mutations were detected in 62.2% of the tumor samples. The most frequently mutated genes were FGFR3 (49.7%) and TP53 (16.2%). No mutation was observed in the WWOX gene. FGFR3 mutations, contrary to TP53, correlated with lower tumor stage and grade, and the presence of multiple tumors. The risk of death was significantly higher in patients with TP53 mutant tumors (HR=3.12; 95%CI: 1.14-7.27; p=0.006) but lower in patients with FGFR3 mutations (HR=0.36; 95%CI: 0.15-0.87; p=0.002). None of the investigated genes was an independent predictor of disease-specific survival, recurrence-free survival or progression-free survival. The results confirm the existence of two alternative pathways of bladder cancer. However the presence of a high percentage of wild type variants in the higher stages of the disease suggest the existence of another pathway of molecular changes leading to the development of bladder cancer. Molecular analysis may have prognostic value and may facilitate the assignment of patients to appropriate forms of treatment - especially in the case of patients with a T1 tumor, where different mutational patterns were observed in each grade.

Opioid-free anesthesia: what about patient comfort? A prospective, randomized, controlled trial.

BACKGROUND: We investigated the effect of a pern-operative opioid-free approach on postoperative patient comfort in patients undergoing breast cancer surgery. SUBJECTS AND METHODS: From September 2014 to July 2015, 66 female patients of the Belgian Oncology Institut Jules Bordet were recruited. They were randomized into two groups: the first group received anesthesia with opioids for their breast cancer surgery, and the second group received opioid-free anesthesia. Patient comfort was evaluated 24 hours postoperatively through the QoR-40 score, with a difference of 15 points considered as being clinically relevant. Postoperative analgesia was provided through a piritramide patient-controlled analgesia device, during the first 24 hours. The hypothesis of this study was that opioid-free anesthesia would improve quality of recovery after anesthesia. RESULTS: A statistically significant difference in postoperative QoR-40 score was observed between groups [Mean (SD) QoR-40 of 182.1/200 (13.9) in the opioid-free group, and 175.6/200 (14.80) in the opioid group; P = 0.04]. The clinical relevance of this finding is questionable, insofar as the difference of 15 points was not met. A statistically significant difference in postoperative piritramide usage was observed (8.1 (6.6) in the opioid-free group, and 13.1 (9.4) in the opioid group; P = 0.03). CONCLUSIONS: This randomized controlled trial shows, for the first time, equal comfort during the immediate postoperative period in patients having received opioid-free and conventional anesthesia for their breast cancer surgery. Opioid-free anesthesia in this indication appears safe, and may be associated with slightly reduced pain during the first 24 postoperative hours.

Extra-media thickness and epicardial fat: Comparison of a novel carotid artery ultrasound index and a well-established cardiac magnetic resonance fat quantification method.

BACKGROUND AND AIM: Epicardial and pericardial fat are well-established surrogate markers of cardiovascular diseases and complications. Extra-media thickness (EMT) is a novel ultrasound index corresponding to arterial adventitia and adipose tissue. We aimed to evaluate the association between carotid EMT and epicardial fat (EF) and pericardial fat (PF) and their relation to cardiovascular risk and metabolic syndrome (MS). METHODS AND RESULTS: One hundred consecutive patients (age: 51.7 ± 15.4 years; males 70%) scheduled for cardiac magnetic resonance (CMR) were prospectively included in the study. Anthropometric parameters, CMR indices of EF and PF, both common carotid arteries EMT, and ultrasound indices of visceral and subcutaneous fat were measured in patients. In our study group, 53% of patients represented a very high cardiovascular risk, overweight or obesity was found in 68%, high body fat in 45%, and MS in 59% of individuals. Mean EMT (662 ± 129 µm) was significantly associated with EF area (r = 0.46; p < 0.001) and PF area (r = 0.3; p < 0.001). Among all fat indices, only EMT (MS+ 736 ± 140 µm vs. MS-658 ± 97 µm; p = 0.002) and EF area (MS+ 870 ± 451 mm(2) vs. MS 668 ± 333 mm(2); p = 0.02) were significantly increased in patients with MS compared with individuals without MS. Multivariable regression analysis also showed that mean EMT is independently associated with number of cardiovascular risk factors (b = 0.005; p < 0.001). Moreover, very high cardiovascular risk subjects showed significantly increased EMT/BMI (p < 0.001) and EF area/BMI (p = 0.03) ratios. However, there was no significant association between EMT/BMI and EF area/BMI values (p = ns). CONCLUSIONS: Our study showed the first findings on the relations between a novel ultrasound index EMT and EF assessed in a reference method of CMR. Carotid EMT may be a new surrogate marker, including both periarterial fat as a major component and arterial adventitia, which may provide additional data on cardiometabolic risk beyond that derived form a well-established EF alone.

A personalised approach to prostate cancer screening based on genotyping of risk founder alleles.

BACKGROUND: To evaluate whether genotyping for 18 prostate cancer founder variants is helpful in identifying high-risk individuals and for determining optimal screening regimens. METHODS: A serum PSA level was measured and a digital rectal examination (DRE) was performed on 2907 unaffected men aged 40-90. Three hundred and twenty-three men with an elevated PSA (≥4 ng ml⁻¹) or an abnormal DRE underwent a prostate biopsy. All men were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA and C61G), for four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395 and I157T), for one allele in NBS1 (657del5), for one allele in HOXB13 (G84E), and for nine low-risk single-nucleotide polymorphisms (SNPs). RESULTS: On the basis of an elevated PSA or an abnormal DRE, prostate cancer was diagnosed in 135 of 2907 men (4.6%). In men with a CHEK2 missense mutation I157T, the cancer detection rate among men with an elevated PSA or an abnormal DRE was much higher (10.2%, P=0.0008). The cancer detection rate rose with the number of SNP risk genotypes observed from 1.2% for men with no variant to 8.6% for men who carried six or more variants (P=0.04). No single variant was helpful on its own in predicting the presence of prostate cancer, however, the combination of all rare mutations and SNPs improved predictive power (area under the curve=0.59; P=0.03). CONCLUSION: These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal.

An inherited NBN mutation is associated with poor prognosis prostate cancer.

BACKGROUND: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. METHODS: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ≤ 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.

Expression of NRF2 and NRF2-modulated genes in peripheral blood leukocytes of bladder cancer males.

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is an oxidant-responsive transcription factor involved in induction of antioxidant genes. We assessed NRF2 and selected NRF2-modulated gene expression: glutathione S-transferase A1 and P1 (GSTA1 and GSTP1), mitochondrial superoxide dismutase (SOD2) in blood leukocytes of 51 bladder cancer patients and 90 control males. A significant up-regulation of SOD2 expression (P=0.002) was observed in leukocytes of patients. NRF2 expression was positively correlated with GSTP1 and with SOD2 mRNA level, both in patients and controls. These data suggest disturbances in SOD2 transcription in circulating blood leukocytes of males with bladder cancer. Moreover, concomitant constitutive expression of NRF2 and its target genes may suggest important role of NRF2 transcription factor in positive regulation of antioxidant genes, resulted in enhanced cytoprotection in human peripheral blood leukocytes.

Calosphaeria Canker of Sweet Cherry Caused by Calosphaeria pulchella in California and South Australia.

California is the second largest sweet cherry producer in the United States with annual revenues up to $200 million. The South Australian cherry industry generates about 10% of Australia's overall production with approximately 1,500 metric tons of cherries produced yearly. In California, perennial canker diseases and subsequent branch dieback are responsible for extensive damage throughout sweet cherry orchards, reducing annual yields and tree longevity. Surveys of cherry orchards and isolation work were conducted in California to identify the main canker-causing agents. Calosphaeria pulchella was the main fungus isolated from cankers, followed by Eutypa lata and Leucostoma persoonii, respectively. Preliminary surveys in cherry orchards in South Australia documented C. pulchella and L. persoonii in cankers. The pathogenicity of C. pulchella in sweet cherry was confirmed following field inoculations of 2- to 3-year-old branches. C. pulchella was able to infect healthy wood and produce cankers with as much virulence as E. lata or L. persoonii. Spore trapping studies were conducted in two sweet cherry orchards in California to investigate the seasonal abundance of C. pulchella spores. Experiments showed that rain and sprinkler irrigation were important factors for aerial dissemination. Finally, this study illustrates the symptoms and signs of the new disease Calosphaeria canker.

Less advanced testicular dysgenesis is associated by a higher prevalence of germ cell neoplasia.

There is a theory that the more evident clinical signs of testicular dysgenesis, the more frequent the neoplastic lesions are. The aim of this study was to relate the incidence of testicular germ cell neoplastic lesions (overt germ cell tumours--GCT or testicular carcinoma in situ) to the intensity of testicular organogenesis disturbances (dysgenesis). Biopsies were taken from 154 testes of the following patients: 23 patients with GCT in the contralateral gonad (CGCT), 41 patients with undescended testes operated in childhood (UDT), 90 with azoo-/oligozoospermia (A/O) diagnosed because of infertility. Assessment of seminiferous epithelium, number of Leydig cells, areal fraction of intertubular space (IS), morphometric analysis of seminiferous tubules diameter and thickness of tubular wall were performed. Monoclonal antibodies against placental like alkaline phosphatase and cytokeratin 18 were applied. Germ cell neoplastic lesions were detected in 7.1% of testes and were associated with disturbed spermatogenesis. Among testes with disturbed spermatogenesis they were found the most frequently in CGCT (22.2% vs. 11.1% in UDT and 3.8% in A/O), where spermatogenesis had the highest score (5.7 +/- 3.8 points vs. 4.2 +/- 2.7 in UDT and 4.6 +/- 2.9 in A/O). In CGCT, signs of testicular dysgenesis were less advanced: the highest tubular diameter was 164.4 +/- 32.3 microm vs. 163.5 +/- 28.6 in UDT and 161.4 +/- 31.5 in A/O, the lowest thickness of tubular wall was 8.9 +/- 3.2 microm vs. 10.2 +/- 3.6 in UDT and 10.2 +/- 3.2 in A/O, lowest IS was 36.9 +/- 14.9% vs. 47.9 +/- 18.0 in UDT and 46.5 +/- 18.5 in A/O, and the lowest percentage of tubules with immature Sertoli cells was 0.1 +/- 0.4% vs. 4.9 +/- 7.0 in UDT and 5.2 +/- 9.7 in A/O. Results indicate that neoplastic lesions appear only in testes with disturbed spermatogenesis. Worse condition of spermatogenesis is associated by the presence of other dysgenetic features, but neoplastic lesions appear more frequently in testes with the less advanced features of testicular dysgenesis.

Perioperative acute coronary syndrome during functional endoscopic sinus surgery in a young HIV-infected patient. A case report.

We report a case of a young HIV-infected woman treated for more than ten years by highly active antiretroviral therapy, presenting a peroperative acute coronary syndrome caused by a hypertensive episode after systemic resorption of locally applied epinephrine during a functional endoscopic sinus surgery. Since patients with multiple risk factors for coronary artery desease seems to be more susceptible to complications of epinephrine injection, this reminds us of the higher cardiovascular risk for HIV patients with long term treatment. Therefore anesthesiologists should be susceptible to consider specifically the pre- and postoperative evaluation of patients with long term antiretroviral therapy.

Desflurane consumption with the Zeus during automated closed circuit versus low flow anesthesia.

INTRODUCTION: During automated closed-circuit anesthesia (CCA), the Zeus (Dräger, Lübeck, Germany) uses a high initial fresh gas flow (FGF) to rapidly attain the desired agent and carrier gas concentrations, resulting in a desflurane consumption well above patient uptake. Because both FGF and carrier gas composition can affect consumption, we determined the Zeus' agent consumption with automated CCA and with automated low flow anesthesia (LFA) (= maintenance FGF of 0.7 L min(-1)) with 3 different carrier gases. METHODS: After IRB approval, 65 ASA PS I or II patients undergoing general surgery received desflurane in either O2, O2/air, or O2/N2O, with the Zeus to maintain the end-expired concentration (FA) at 6, 6, and 4% and the F1O2 at 1.0, 0.6, and 0.4, respectively. In addition, patients were assigned to either automated CCA (O2 n = 11; O2/air n = 11; O2/N2O n = 11) or automated LFA (selected FGF 0.7 L min(-1)) (O2 n = 12; O2/air n = 11; O2/N2O n = 9). Demographics and desflurane consumption at 2, 4, 6, 8, 10, 20, 30, 40 and 50 min were compared. RESULTS: With the same carrier gas, desflurane consumption was lower with the CCA mode than with LFA mode after 4 min in the O2 groups, 6 min in the O2/air groups, and 30 min in the O2/N2O groups. Within each mode, desflurane consumption in the O2 and O2/air groups was identical at all times. Despite the use of a lower FA in the N2O groups, initial desflurane consumption was higher than in the O2 and O2/air groups, but it was lower later (> or = 15 min) only with LFA. DISCUSSION: After 50 min, desflurane consumption with automated CCA is lower than with automated LFA. However, initial agent consumption is complex, and N2O in particular may increase initial desflurane consumption (though ultimately resulting in lower desflurane usage because of its MAC sparing effect) because initial FGF is increased to rapidly reach the target concentrations. Differences in desflurane consumption only become apparent after FGF has stabilized to the target FGF.

The influence of climate on foliar symptoms of eutypa dieback in grapevines.

ABSTRACT Foliar symptoms of Eutypa dieback, caused by Eutypa lata, in grapevines, cv. Shiraz, varied from year to year in a 6-year study conducted in South Australia and, although trends were similar for vineyards within geographical regions, differences were observed between regions. We attempted to elucidate the causes underlying this variation and hypothesized that it was influenced by climatic factors. A number of possible relationships were identified between climate and symptom expression: (i) increased symptom expression was related to increased winter rainfall 18 months earlier, (ii) decreased disease incidence and prevalence were related to increased temperature in spring, and (iii) a reduction in disease incidence was related to both very high and very low rainfall in October. Theories for these relationships are proposed and require further investigation. A conceptual model was developed which requires validation and has the potential to predict the incidence of foliar symptoms of Eutypa dieback. Information from this study could lead to an improved integrated pest management system to suppress foliar symptoms and sustain productivity of vines infected with E. lata.

A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.

BACKGROUND: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. PARTICIPANTS AND METHODS: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. RESULTS: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G-->A, 1100delC). CONCLUSION: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.

The Influence of Grapevine Cultivar and Isolate of Eutypa lata on Wood and Foliar Symptoms.

Grapevine cultivar (Vitis vinifera) and isolate of Eutypa lata influence wood and foliar symptoms of Eutypa dieback. Foliar symptoms of Eutypa dieback developed within 8 months of inoculating young grapevines (cvs. Grenache, Cabernet Sauvignon, and Merlot) in a shadehouse. Isolates of E. lata from various wine regions in southern Australia varied in their ability to colonize inoculated grapevines and induce wood and foliar symptoms. Grapevine cultivars varied for wood and foliar symptom expression but not for mycelial colonization. However, the severity of foliar symptoms was not related to the rate of spread of the fungus in the grapevine. Furthermore, the staining of wood typically attributed to E. lata did not reflect the presence of the fungus because the fungus was detected up to 80 mm beyond the stain. A field trial with mature grapevines revealed significant differences in the rate of spread of wood staining due to E. lata among eight cultivars, with up to 50 mm/year detected in Cabernet Sauvignon and Shiraz grapevines. In the shadehouse, the maximum growth rate of E. lata was recorded to be 115 mm/year for Grenache rootlings. Information from this study may help to optimize management strategies for maintaining productivity of grapevines with Eutypa dieback, thus reducing the economic impact of the disease.

The effect of analgesic state on implicit learning during propofol anesthesia in volunteers.

Noxious stimulation may enhance implicit learning during general anesthesia. It is unknown, however, whether analgesic state can influence this memory processing. Twenty healthy adult volunteers were enrolled our prospective, double-blinded, controlled experiments. Anesthesia was induced with a propofol target controlled infusion (TCI), titrated in step-wise increments to loss of consciousness. In phase A, a 10-word list was played to the subjects while a noxious stimulus was applied (hand immersion in cold water at 2-4 degrees C). In phase B, a remifentanil TCI infusion was added to the steady-state propofol TCI anesthesia, and titrated to loss of hand movement on cold water immersion. A second 10-word list was then played while maintaining the hand in cold water. Memory testing, 2 hours post-recovery revealed no evidence of explicit memory in any subject during either phase of the study. During phase A, the word stem completion test revealed implicit learning for played words. In contrast, no implicit memory was detected during phase B. This study indicates that analgesia with remifentanil TCI (titrated to loss of movement on noxious stimulation), prevented implicit memory processing during stable propofol anesthesia in healthy adult volunteers.

MMP, VEGF and TIMP as prognostic factors in recurring bladder cancer.

OBJECTIVES: To investigate the clinical correlates and prognostic utility of MMP, VEGF and TIMP genes expression in bladder cancer (BCa) recurrence. METHODS: Expression of MMP1, MMP2, MMP9, VEGFA and TIMP1, TIMP3 was analyzed by qRT-PCR using SYBR Green in peripheral blood leukocytes (PBLs) of BCa patients at two time points (diagnosis (n=40), and first recurrence (n=40)) and an age-matched group of healthy controls (n=100). Plasma concentrations of MMP1 (pro- and active forms) were measured using ELISA in BCa patients. RESULTS: The expression of MMP1 mRNA was significantly lower in BCa patients with first recurrence compared to control (p=0.019). Expression of other genes did not differ significantly between the groups. MMP9 gene expression was associated with differentiation grade (p=0.043), with the highest expression in poorly differentiated tumors (G3) and was higher in smokers than in non-smokers (p=0.039) in BCa patients at diagnosis. The results at two time points showed that MMP9 and VEGFA genes expression was increased in patients with moderately differentiated BCa (p=0.029), and advanced pathologic stage (p=0.048), respectively. Moreover, gene expression of TIMP1 was increased for G3 (p=0.043), and was decreased for early recurrence (p=0.003). CONCLUSIONS: Our study suggests that the expression of MMP9 in PBLs of BCa patients at diagnosis is associated with the differentiation grade of the BCa, and smoking status. Genes expression of MMP9, VEGFA and TIMP1 in PBLs may play a pivotal role in regulation of progression of BCa. Additionally, TIMP1 gene expression may be important factor for early recurrence of BCa.

The role of spinal and brainstem adenosine receptors in the modulation of the volume-evoked micturition reflex in the unanesthetized rat.

The pharmacology of the spinal, supraspinal and peripheral adenosine receptor subtypes (A1, A2) and their influence on the volume-evoked micturition reflex (VEMR) was studied in a chronic unanesthetised rat model by cystometrography after intrathecal (i.t.), intracerebroventricular (i.c.v.) and intravenous (i.v.) injection. Intrathecally administered A1 adenosine agonist: N6-(L-2-phenylisopropyl)adenosine (R-PIA) and A2 adenosine agonist: 5'-(N-ethylcarboxamido)adenosine (NECA) were equally active with 1.0 nmol reliably producing an increase in the volume necessary to induce the VEMR. At a higher dose (3 nmol), a long-lasting blockade of the VEMR was produced by both agonists. These effects were reversed following intraperitoneal injection of caffeine, an adenosine antagonist. This inhibition of the VEMR outlasted the spinal antinociceptive action which we have previously reported for these two agonists. Contrary to the spinal effect of these agonists, i.c.v. (0.3-3 nmol) and i.v. (100-1000 nmol) injections of R-PIA and NECA resulted in a significant decrease in the volume required to evoke the VEMR. We conclude that at the spinal level a xanthine-sensitive adenosine receptor(s) inhibits the VEMR. Based on several indirect lines of evidence, we speculate that these effects are not mediated by an action on primary afferent input or directly on preganglionic neurons, but on an excitatory interneuronal link.

Spinal administration of receptor-selective drugs as analgesics: new horizons.

The processing at the spinal cord levels of sensory information is subject to modulation by a number of local receptor systems, including opioids: alpha 2 adrenergic; and to a lesser extent serotonin, GABAB, neuropeptide Y, cholinergic, adenosine, and the NMDA-glutamate site. The functional utility of these multiple systems are only partially understood, but it appears that (a) they may act individually to alter different aspects of the nociceptive sensory message (b) they could be used synergistically to reduce the incidence of side effects by reducing the dose of agents required to yield analgesic effects, and (c) they may function variably in animals made tolerant to classes of receptor agonists.

Gutron treatment of patients suffering from essential orthostatic hypotony. Part Two--Autonomic system investigation.

Neurovegative control of circulatory system in essential orthostatic hypotony (EOH) is not well recognized. Therefore, in group of 9 patients (pts) with EOH treated with midodrine (Gutron, Gu) 5 mg i.v. we performed a study of sympathovagal balance, based on heart rate variability (HRV) analysis. From computer-assisted tachograms we calculated standard deviation of 512 sinus cycles length (SD-SCL) and from power spectral analysis by fast Fourier transformation we derived: amplitudes of high frequency (HF, 0.15-0.35 Hz) and low frequency (LF, 0.05-0.15 Hz) spectra, percentage of power of HF and LF spectra and their ratio, named vegetative control coefficient (VCC, %LF:%HF). Results were compared to that received from control group (11 volunteers). We found that EOH-pts presented lower amplitude of HF, especially after Gu, a lack of increment of %LF irrespective to treatment and higher VCC, which normalized to control value after Gu. We stated that: 1) both branches of autonomic system are disturbed in EOH-patients; 2) Gutron shifts sympatho-vagal balance from initial resting sympathicotomy into parasympathetic predominance.