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Provenance trials provide a valuable opportunity to evaluate the impact of extreme events on growth and wood properties. In this study, we have evaluated 81 Norway spruce provenances, tested in three provenance trials established in the Romanian Carpathians in 1972. The response to drought of the Norway spruce provenances has been examined using the following tree resilience indices: resistance, recovery, resilience, and relative resilience. The relationship between climate and growth, the correlations between wood traits, and the coordinates of the origin and tree resilience indices were also analysed. In each provenance trial, there were significant differences between provenances and years regarding wood widths and latewood percentage (LWP). Regarding drought extreme events, the years when they occurred in all three provenance trials were 2000 and 2003. Significant differences between provenances for at least one tree resilience index have been found in all provenance trials, for the year 2000. By using subperiods of 25 years, changes in the relationship between climate and growth have been observed. Several provenances with high radial growth and good resistance and/or recovery have been identified. Provenances that performed better in common garden experiments could be used in assisted migration, even in the proximity of the current natural range.

Plastic pollution is a global concern that has a significant impact on marine life. Plastic is widely used and has become a pervasive pollutant in marine environments. Plastic contamination has been documented both in marine environments and biota. Plastic contamination in cetacean gastro-intestinal tract (GIT) content has received limited attention, especially in the Black Sea. This study aims to investigate plastic contamination in the GITs of bottlenose dolphins and harbour porpoises, introducing a novel methodology. Given the limited exploration of this issue in the Black Sea, the research predominantly focuses on microplastic contamination. The GITs were sampled through necropsy from stranded and by-caught cetaceans, and content was washed through a multi-sieves tool. The material retained on each sieve was analysed following specific protocols. All (100%) of the GITs contained plastics (meso- and microplastics). In total, 1059 items (fibres, fragments, and beads) ranging from 22.86 µm to 5776 µm were found, suggesting a high contamination level in the Black Sea cetaceans. Future efforts should concentrate on increasing the number of samples and using the results for the implementation of the Marine Strategy Framework Directive (MSFD).

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-β2 glycoprotein I antibodies (aβ2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aβ2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases ( p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer ( p = 0.016), aPTT ( p = 0.001), ferritin ( p = 0.012), C-reactive protein (CRP) ( p = 0.027), lymphocyte ( p = 0.040), and platelet ( p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Environmental DNA (eDNA) metabarcoding is an effective method for studying fish communities but allows only an estimation of relative species abundance (density/biomass). Here, we combine metabarcoding with an estimation of the total abundance of eDNA amplified by our universal marker (teleo) using a quantitative (q)PCR approach to infer the absolute abundance of fish species. We carried out a 2850-km eDNA survey within the Danube catchment using a spatial integrative sampling protocol coupled with traditional electrofishing for fish biomass and density estimation. Total fish eDNA concentrations and total fish abundance were highly correlated. The correlation between eDNA concentrations per taxon and absolute specific abundance was of comparable strength when all sites were pooled and remained significant when the sites were considered separately. Furthermore, a nonlinear mixed model showed that species richness was underestimated when the amount of teleo-DNA extracted from a sample was below a threshold of 0.65 × 10 6 copies of eDNA. This result, combined with the decrease in teleo-DNA concentration by several orders of magnitude with river size, highlights the need to increase sampling effort in large rivers. Our results provide a comprehensive description of longitudinal changes in fish communities and underline our combined metabarcoding/qPCR approach for biomonitoring and bioassessment surveys when a rough estimate of absolute species abundance is sufficient., (© 2022 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

The ability of bacteria to degrade organic pollutants influences their fate in the environment, impact on the other biota and accumulation in the food web. The aim of this study was to evaluate abundance and expression activity of the catabolic genes targeting widespread pollutants, such as polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and hexachloro-cyclohexane (HCH) in the Black Sea water column and sediments. Concentrations of PAHs, PCBs and HCH were determined by gas chromatography (GC) coupled to mass spectrometry (MS) and electron capture (ECD) detectors. bphA1, PAH-RHDα, nahAc, linA and linB that encode biphenyl 2,3 dioxygenase, α-subunits of ring hydroxylating dioxygenases, naphthalene dioxygenase, dehydrochlorinase and halidohydrolase correspondently were quantified by quantitative PCR. More recalcitrant PAHs, PCBs and HCH tended to accumulate in the Black Sea environments. In water samples, 3- and 4-ringed PAHs outnumbered naphthalene, while PAHs with > 4 rings prevailed in the sediments. Congeners with 4-8 chlorines with ortho-position of the substituents were the most abundant among the PCBs. β-HCH was determined at highest concentration in water samples, and total amount of HCH exceeded its legacy Environmental Quality Standard value. bphA1, was the most numerous gene in water layers (10 5 copies/mL) and sediments (10 5 copies/mg), followed by linB and PAH-RHDα genes (10 3 copies/mL; 10 5 copies/mg). The least abundant genes were linA (10 3 copies/mL; 10 4 copies/mg) and nahAc (10 2 copies/mL; 10 4 copies/mg). The most widely distributed gene bphА1 was one of the least expressed (10 -3 -10 -2 copies/mL; 10 -1 copies/mg). The most actively expressed genes were linB (10 1 -10 2 copies/mL; 10 3 copies/mg), PAH-RHDα (10 1 copies/mL; 10 2 copies/mg) and linA (10 -1 -10 0 copies/mL; 10 0 copies/mg). Interaction of bacteria with PAHs, PCBs and HCH is evidenced by high copy numbers of the catabolic genes that initiate their degradation. More persistent compounds, such as high-molecular weight PAHs or β-HCH are accumulating in the Black Sea water and sediments, albeit microbial activity is directed against them., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives : GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods : Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results : The median age was 61 years (range, 28-78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm ( p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones ( p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors ( p = 0.0001) and in cases with Ki67 ≥ 50% ( p = 0.008). Conclusions : PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs.

The Black Sea is the largest semi-closed permanently anoxic basin on our planet with long-term stratification. The study aimed at describing the Black Sea microbial community taxonomic and functional composition within the range of depths spanning across oxic/anoxic interface, and to uncover the factors behind both their vertical and regional differentiation. 16S rRNA gene MiSeq sequencing was applied to get the data on microbial community taxonomy, and the PICRUSt pipeline was used to infer their functional profile. The normoxic zone was mainly inhabited by primary producers and heterotrophic prokaryotes (e.g., Flavobacteriaceae, Rhodobacteraceae, Synechococcaceae) whereas the euxinic zone-by heterotrophic and chemoautotrophic taxa (e.g., MSBL2, Piscirickettsiaceae, and Desulfarculaceae). Assimilatory sulfate reduction and oxygenic photosynthesis were prevailing within the normoxic zone, while the role of nitrification, dissimilatory sulfate reduction, and anoxygenic photosynthesis increased in the oxygen-depleted water column part. Regional differentiation of microbial communities between the Ukrainian shelf and offshore zone was detected as well, yet it was significantly less pronounced than the vertical one. It is suggested that regional differentiation within a well-oxygenated zone is driven by the difference in phytoplankton communities providing various substrates for the prokaryotes, whereas redox stratification is the main driving force behind microbial community vertical structure., (© 2021 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

As the largest semi-closed marine ecosystem in the world, the Black Sea has been heavily affected by human activities for a long time. Describing the biodiversity of multi-trophic biota in pelagic zone of the Black Sea and identifying the dominant environmental factors are prerequisites for protecting the sustainability of ecosystems. However, up to now, the taxonomic and distributional information about the Black Sea biota is not clear. Here, we employed a Tree-of-Life metabarcoding to analyze the biodiversity of eight communities in the Black Sea, investigated their biogeographical distribution, and further analyzed the influence of biological and abiotic factors on biota on large scales. We found that, (1) Over 8900 OTUs were detected in the Black Sea, of which 630 species were identified, covering the holistic biota from single-celled (bacteria 5620 OTUs 141 species; algae 1096 OTUs 185 species; protozoa 546 OTUs 146 species) to multicellular organisms (invertebrate metazoans 150 OTUs 34 species; fishes 1369 OTUs 76 species; large marine mammals 39 OTUs 5 species). (2) Higher trophic organisms (fishes and large mammals) distributed more evenly in space than the lower (microorganisms, protozoa and invertebrates). For lower trophic organisms, the vertical stratification was more obvious than the horizontal stratification (vertical p < 0.02, horizontal p < 0.05). (3) The bottom trophic organisms (bacteria and algae) of the food web significantly affected the distribution and composition of the others through biological interactions (Mantel p < 0.05). (4) At the level of abiotic factors, the effect of local species sorting on the composition of communities was 15% higher than that of mass dispersal effect. For the first time, this study monitored and profiled the holistic biodiversity in the pelagic zone of the Black Sea, and provided technological advances and preliminary knowledge for the ongoing Black Sea ecosystem protection efforts., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In Romania, 23 patients have been diagnosed with hereditary transthyretin amyloidosis (ATTRh), 18 of whom have the Glu54Gln mutation. This retrospective cohort included all patients with Glu54Gln-mutated ATTRh who were diagnosed in Romania from 2005 to 2018., Results: Of 18 patients, 10 were symptomatic, five were asymptomatic carriers and three died during the study. All originated from North-East Romania. Median age at symptom onset was 45 years; median age at death was 51 years. All patients had cardiac involvement, including changes in biomarkers (mean N-terminal-pro B-type natriuretic peptide: 2815.6 pg/ml), electrocardiography (15% atrial fibrillation, 38% atrioventricular block, 31% right bundle block), and echocardiography (mean interventricular septum: 16 mm, mean left ventricular ejection fraction: 49%). Scintigraphy showed myocardial radiotracer uptake in all patients. In addition, 92% of patients had polyneuropathy at diagnosis and 53% had carpal tunnel syndrome; 69% exhibited orthostatic hypotension and 31% suffered from diarrhea. No renal or liver involvement was observed., Conclusions: This is the largest Glu54Gln-mutated ATTRh cohort diagnosed to date, and to our knowledge the first describing this variant worldwide. Clinical features of this variant are early onset, neurological and cardiac involvement, aggressive disease progression and short survival. Early diagnosis and therapeutic intervention have potential to improve prognosis in ATTRh.

Rationale: Acute ST-segment elevation myocardial infarction (STEMI) is a rare complication of acute ischemic stroke (AIS) during thrombolytic therapy. We report a case of STEMI occurring 40 minutes after thrombolytic therapy for AIS and discuss the possible mechanisms and therapeutic approaches., Patient Concerns: A 87-year-old woman with a history of arterial hypertension was admitted for acute onset of right-sided limb weakness 2 hours before arrival at the emergency department. Forty minutes after intravenous recombinant tissue plasminogen activator (i.v. rtPA) administration for AIS, STEMI occurred (signaled by a third-degree atrioventricular block)., Diagnoses: The diagnoses were AIS and STEMI. Coronary angiography confirmed right coronary artery occlusion., Interventions: Four hours after the onset of STEMI, stenting was performed, normalizing the coronary blood flow., Outcomes: The patient died 2 days thereafter because of persistent cardiogenic shock., Lessons: Our case is remarkable owing to the unusually early (<1 hour) occurrence of STEMI after i.v. rtPA administration. A third-degree atrioventricular block after thrombolysis for AIS could signal a STEMI onset. New and ongoing trials are assessing whether adjunct administration of direct thrombin inhibitors of rtPA in the first 24 hours after thrombolysis for AIS can prevent early recurrent ischemic events.

Context: Carcinoid tumors arising from the bile ducts account for only a small fraction of biliary tract cancers., Case Report: We report herein a 42-year-old man with a carcinoid tumor of the common bile duct. He presented with abdominal pain, bloating and dyspepsia. Clinicolaboratory and imaging studies suggested a probable obstructive common bile duct lesion. The patient underwent an endoscopic retrograde cholangiopancreatography with a stent placement in view of common bile duct decompression. Persistence of symptoms prompted a laparotomy and pancreaticoduodenectomy that revealed a well-differentiated carcinoid tumor originating in the common bile duct., Conclusion: Clinician's familiarity with the unusual sites of origin of neuroendocrine tumors and/or atypical presentation of such tumors may facilitate their early recognition and allow for a timely intervention.

Pheochromocytomas rarely have 'composite' forms in which they demonstrate histologic features of a typical paraganglioma in combination with those of a neural component. Extra-adrenal 'composite' pheochromocytomas are distinctly uncommon. We describe herein a unique case of a 34-year-old female patient with type 1 neurofibromatosis who presented with abdominal pain and paroxysmal hypertension. Imaging revealed a pancreatic mass with biliary and pancreatic ductal dilatation and a hormonal assay led to the diagnosis of functional pheochromocytoma. She underwent surgical resection and histopathology revealed a composite paraganglioma-ganglioneuroma. Clinical, biochemical and radiological aspects of this rare tumor and its association with neurofibromatosis and other hereditary cancer syndromes are discussed., (Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Several chemotherapy agents and combinations have proven effective in the therapy of advanced enteropancreatic neuroendocrine tumors (EP-NETs). However, their toxicity can be significant. Recent understanding of the molecular mechanisms of these tumors, especially the central role of tumor angiogenesis, has led to the identification of new therapeutic targets and agents directed at the molecular level., Areas Covered: This paper gives a comprehensive evaluation of the existing therapeutic armamentarium for EP-NETs. Narrated in a historical perspective, this review analyzes the available information on traditional chemotherapy agents, interferon-α and somatostatin analogs, as well as newer therapies and experimental agents., Expert Opinion: Despite recent advances, a curative approach for metastatic EP-NETs is yet to be discovered. To date, sunitinib and everolimus have been shown to impact progression-free survival only in pancreatic NETs, and the duration of this benefit has not yet been established. Further research is necessary to determine whether a combination of these drugs, either together or with other therapies, may yield superior outcomes. Moreover, sequential use of these agents should be explored in an attempt to improve survival. Efficacy of a variety of experimental agents is also being tested in clinical trials.

Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of tumors, having their origin in cells of diffuse endocrine system, with particular clinical course, diagnosis and treatment., Patients and Methods: In our study, were included 68 patients with neuroendocrine digestive tumors admitted, diagnosed and treated in Fundeni Clinical Institute, Bucharest, in the last ten years--2000-2010 (retrospective study)., Results: Thirty-three (49%) patients were males, 35 (51%) females, and the main age was 58.9 years. In 62 (90.3%) cases was possible to find the primary tumor. The examined tumors had different localizations: pancreas--32 (47.04%) cases (head--17 (24.99%) cases, and body and tail--15 (22.05%) cases), stomach--7 (10.29%) cases, small intestine--7 (10.29%) cases, 6 (8.82%) cases--unknown primary site (diagnosis was established on metastases), right colon--6 (8.82%) cases, liver--6 (8.82%) cases, rectum--2 (2.94%) cases, and retroperitoneum--2 (2.94%) cases. Microscopic examination revealed 59 (86.8%) malignant tumors and 9 (13.2%) benign tumors. Using WHO 2000 Classification, 28 cases of malignant tumors were well-differentiated neuroendocrine carcinomas, and 31 cases were poor differentiated neuroendocrine carcinomas. From malignant cases, 25 (42.3%) have distant metastases and 15 (25.9%) lymph node metastases., Conclusions: Cases of gastroenteropancreatic neuroendocrine tumors included in our study had clinical and histopathological features in correspondence with data from literature--slight predominance in women, predominance in 5th and 6th decades of life, the most frequent localizations were at pancreatic level--both head and body and tail, but the rarest were in colon and retroperitoneum. Most of the cases studied, were malignant tumors, from these more than a half were poor differentiated, and a quarter of them having lymph node or distant metastases.

Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

Objectives: The aim of this study was to evaluate the association between interleukin (IL)-6 and IL-10 gene polymorphism and the short-term risk of postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgery and also to evaluate the endothelial function., Methods and Results: We determined preoperatively IL-6 gene polymorphism (-174 G/C and nt565 G/A), IL-10 polymorphism (-1082G/A, -819C/T, -592C/A), and brachial artery vasodilatation using ultrasound in 48 patients undergoing vascular surgery. Eight patients (16.7%) developed over a period of 30 days cardiovascular events (cardiovascular death, resuscitated cardiac arrest, acute myocardial infarction, unstable angina, stroke). Cardiovascular events were more frequent in the subgroups of patients with genotypes associated with high serum levels of IL-6: -174CC (57.14% vs 12.5% for -174GC genotype and 8% for -174GG, P = .007) and nt565AA (50% vs 17.6% for nt565GA genotype and 8% for nt565GG genotype, P = .021) and in subgroups with haplotypes associated with low serum levels of IL-10: ATA (57.14% vs 14.8% for haplotype ACC and 7.4% for GCC, GCA, GTA, GTC haplotypes, P = .004). Flow-mediated dilatation was significantly lower in patients with IL-6 -174CC genotype (7.05% +/- 1.49% vs 8.41% +/- 1.9% for IL-6 -174GC and 9.42% +/- 2.46% for IL-6 -174GG, P = .009) and IL-6 nt565AA genotype (7.14 +/- 1.61% vs 8.49% +/- 1.91% for IL-6 nt565GA and 9.42% +/- 2.46% for IL-6 nt565GG, P = .018) and in patients with IL-10ATA haplotype (6.45% +/- 0.57% vs 9.13% +/- 2.52% for IL-10ACC and 9.24% +/- 2.09% for IL-10 GCC/GCA/GTA/GTC, P = .004) respectively., Conclusions: IL-6 -174CC and nt565AA genotypes and IL-10ATA haplotypes are correlated with a high short-term risk of acute postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgical revascularization and with endothelial dysfunction in these patients., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

We propose a cross-species approach for assigning Gene Ontology terms to LocusLink genes based on evidence extracted from biomedical journal articles. We make use of information from orthologous genes to derive and merge two sets of GO codes for a given target gene. For the first set, we restrict GO code assignments to be selected from only those codes which have already been assigned to the target gene's ortholog. Since this approach results in high precision but low recall, for the second set, we allow any GO code to be a candidate, but then eliminate those codes which are illogical to pair with a GO code that is known to be associated with the orthologous gene. Experimental results on three datasets show that the F-measure obtained with this algorithm is consistently higher than the F-measure of other current solutions.

We have chosen this case of sporadic atrial myxoma for our presentation because it had a particular evolution, with recurrence at 8 years after surgical excision (echocardiography was performed every year) and a particular diagnostic means - at echocardiographic follow-up, the patient being asymptomatic. This presentation, together with a review of literature included in the article, emphasizes the importance of a careful postoperative follow-up of the patients and the existence of some particular aspects of the evolution and symptomatology of recurrent atrial myxoma.

The catecholamine (CA) response to upright posture was studied in 30 brainstem infarct patients with orthostatic arterial hypotension; the investigation was made before and after 10 days propranolol therapy (in 15 cases) and before and after 10 days metoclopramide therapy (in other 15 cases). Before treatment almost all patients responded to posture by a rise in adrenaline (A) excretion and by a depression in noradrenaline (NA) excretion. Propranolol therapy prevented the excessive A release produced by standing and normalized their NA response to posture. Metoclopramide administration also prevented the post-orthostatic A discharge but had no significant influence on NA response to posture. Both drugs exerted a favourable influence on postural hypotension of investigated patients. As post-orthostatic A discharge observed in patients with postural hypotension is involved in the pathogeny of this syndrome and both metoclopramide and propranolol are able to correct this disorder one may maintain that the clinical favourable results obtained with these drugs are ascribable at least partly to their blocking effect on A release.

The effect of forearm or calf ischemia on computerized EEG was studied in five patients with peripheral nervous system affections and five patients with cerebral infarction. Spatial analysis of power spectra in various frequency bands was performed in two 8-sec epochs, the former before ischemia and the latter after 5-min from the cessation of circulatory arrest which lasted 15 min. Transient peripheral ischemia resulted in consistent augmentation of alpha activity involving both the anterior and the posterior hemispheric areas, bilaterally. On the other hand, the slower frequency bands (theta, delta) underwent minor, nonsignificant alterations after ischemic stress. The rise of alpha amplitude induced by ischemic stress was ascribed to the activation of nonspecific thalamic system. The activation of this system might also be involved in the favourable effects exerted by ischemic stress on motor recovery of paretic limbs.

Catecholamine (CA) response to exercise was studied in patients with common (16 cases) or classic (7 cases) migraine as well as in subjects with lumbar disc disease (20 control cases). In migrainous patients exercise induced constantly a rise in epinephrine (E) urinary excretion and a depression in norepinephrine (NE) excretion; the post-exercise E excretion represented the double or the treble of basal E excretion. In controls the pattern of CA response to exercise was opposite to that noted in migraineurs: the exercise induced in almost all controls an augmentation in NE excretion and a depression in E excretion. The pattern of CA response to exercise of migrainous patients is similar to that noted in them after light exposure. As such patients responded by an E discharge to both exercise and light exposure, two conditions preceding quite often the onset of migraine attack, the data suggest the participation of this biochemical abnormality in the pathogeny of migraine. The interpretation is also supported by our previous data demonstrating that the antimigraine drugs are able to prevent the E discharge induced in migrainous patients by light exposure.

Transient ischemia of the extremities was applied in compression or traumatic neuropathies affecting radial nerve (17 cases), ulnar nerve (3 cases), upper brachial plexus (4 cases) or peroneal nerve (10 cases). The limb opposite to that displaying paresis was submitted repeatedly to a 15-minute-period of ischemia every other day for two weeks. The procedure induced in most patients (27 out of 34 cases) a motor improvement of variable degree. In some patients (13 cases) the motor recovery occurred two days or more after starting the procedures, while in others (14 cases) during the very day in which the initial session of ischemia was made or even during the first hour of procedure application. The most beneficial effects of peripheral ischemia were noted in compression neuropathy of peroneal nerve palsy, 9 out of 10 patients with such a disorder being improved by the procedure. We suppose that the method of therapy proposed by us restores promptly the motility of patients with compression neuropathy by inducing a long-lasting activation of some central neural mechanisms.

The effect of amitriptyline on catecholamine (CA) response to light of 20 migrainous patients was studied. The drug was given orally, 36 mg daily (12 mg x 3), for ten days. Before therapy, the migraineurs responded to light by an increase in epinephrine (E) excretion and not by the rise in norepinephrine (NE) excretion, noticed in controls. The NE excretion of migrainous subjects underwent very often a depression after photostimulation. Amitriptyline therapy prevented the post-photic rise in E excretion of migraineurs, without influencing significantly the variation in NE excretion produced in them by light. In other 8 migrainous subjects the effect of flunarizine, a selective calcium channel blocker, on CA response to light was tested. The dosage was of 5 mg daily, for ten days. Flunarizine had similar effects to those displayed by amitriptyline; the drug prevented the rise in E excretion produced by light without normalizing the NE response to light of migrainous subjects. The results suggest that the efficiency of these two drugs in migraine prophylaxis is connected with the ability of these substances to block the E discharge produced in migraineurs by light or by other stimuli. The interpretation is all the more likely as propranolol, another drug applied in migraine prophylaxis also blocks the post-photic E discharge of migraineurs.

The norepinephrine (NE) and epinephrine (E) responses to forearm ischemia were studied in 24 myasthenic patients and 22 subjects with lumbar disc disease (control group). In some of these myasthenic (11 cases) and control (11 cases) subjects the NE and E responses to orthostasis were also investigated. In controls both stimuli induced a rise in NE urinary excretion without significantly changing the E excretion. On the other hand, in myasthenic patients forearm ischemia and orthostasis were followed by an augmentation in E excretion, the NE excretion remaining unchanged or even undergoing a depression. In other myasthenic patients (10 cases) and subjects with lumbar disc disease (10 cases) NE and E responses to exercise were tested. The results were similar to those presented above: controls reacted to exercise by a rise in NE excretion, while myasthenic patients, by an augmentation in E excretion; the NE excretion underwent no change or even decreased after exercise in myasthenia. The obliteration of NE response to all three testing stimuli found in myasthenic patients may be considered as a sign of their sympathetic deficiency. In such patients the normal E discharge produced by forearm ischemia, orthostasis or exercise may be interpreted as a compensatory reaction, being probably the consequence of sympathetic deficiency. The noradrenergic deficit of myasthenic patients is ascribable to their cholinergic hyperactivity.

The effects of centrophenoxine on catecholamine (CA) response to orthostasis and on postural blood pressure fall of 25 patients with orthostatic hypotension due to brainstem ischemia were studied. Before therapy, the patients responded to posture by a depression in norepinephrine (NE) excretion and a rise in epinephrine (E) excretion. After a 10-day treatment with centrophenoxine, 800 mg daily, the patients responded to posture like normals, i.e. by a rise in NE excretion and a reduction in E excretion. Although the orthostatic blood pressure fall was less marked after treatment, the favourable clinical effect of the drug could not be correlated significantly with the restoration of CA response to posture after treatment.

Norepinephrine (NE) and epinephrine (E) responses to upright posture were investigated in 25 patients with orthostatic hypotension due to brainstem ischemic lesions and in 25 control subjects. In controls the postural stimulus induced constantly a rise in NE urinary excretion and a reduction in E excretion, while in patients with orthostatic hypotension it caused a depression in NE urinary excretion and a rise in E urinary excretion; the last alteration was noticed in all but one patient. The E discharge induced by posture in patients with orthostatic hypotension may be involved in the reduction of vascular peripheral resistance and then in postural fall of blood pressure displayed by such patients.

The catecholamine (CA) response to light before and after propranolol therapy was studied in 25 migrainous subjects. Before therapy an abnormal CA response to light consisting of a rise in epinephrine excretion and a depression in norepinephrine (NE) excretion was noticed in migrainous patients. After propranolol administration (60 mg daily for 10 days) the post-photic augmentation in epinephrine excretion and the post-photic depression in NE excretion no longer occurred. As epinephrine discharge may be pathogenetic for migraine attack, the favorable effect of propranolol in migraine therapy could be due to its ability to prevent the epinephrine release induced by light or other stimuli.

The influence of head down (HD) tilting on brain-stem auditory evoked responses (BAER) was studied in hypertensives with supine brain-stem disorders (occipital headache, vertigo, nausea, diplopia, blurred vision occurring after night recumbency), in hypertensives without such phenomena and in normotensives. In the latter two categories of subjects HD tilting had no effect on BAER. On the contrary, in hypertensives with supine brain-stem disorders the manoeuvre induced a constant prolongation of I-V and III-V intervals and a depression in the amplitude of wave V; the alterations of BAER produced by HD tilting reveal probably a dysfunction of the superior brain-stem area and might be due to the impaired cerebral venous draining subsequent to the manoeuvre. The study of BAER after HD tilting seems to be a proper means to attest the supine brain-stem disorders displayed by some hypertensives.

A method of treatment consisting in administration of a neurodynamic drug, pyrithioxin, combined with a short period of hyperventilation (HV) was applied in cerebral infarct patients with hemiplegia. The combination was superior to pyrithioxin alone for the motor recovery of these patients. In some cases, it induced immediately a partial restoration of motility. The combination constantly brought about an increase in urinary excretion of norepinephrine and vanilmandelic acid, which failed to occur after pyrithioxin or HV alone. HV appears to facilitate the neural effects of the drug by promoting its transfer into the CNS.

Catecholamine urinary excretion under basal conditions and after head down tilting (4 degrees) was studied in normo- and hypertensive controls and in patients with hemisphere and brainstem infarction, respectively. Both the normo- and hypertensive controls and patients with hemisphere infarction displayed a conspicuous decrease (about 40%) in noradrenaline (NA) urinary excretion after head down tilting. In contrast the patients with brainstem infarction increased NA urinary excretion after the manoeuvre, suggesting activation instead of deactivation of the sympathetic nervous system (SNS). In normo- and hypertensive controls the values of night NA excretion were lower than those of day NA excretion, whereas in brainstem infarct patients the night NA excretion was close to the day NA excretion. This finding also supports the view that the brainstem infarct patients are not able to deactivate their SNS during night recumbency. The SNS reactivity disorder of such patients if associated with impairment of autoregulation of cerebral circulation might generate an abnormal increase in cerebral circulation during night recumbency.

The epinephrine (E) and norepinephrine (NE) urinary excretion before and after a mild "emotional stimulus" (ES) was determined in 22 patients with cerebral infarction and 30 patients with cerebral hemorrhage, as well as in 18 normotensive and 18 hypertensive controls. In patients with cerebral infarction, the majority normotensive, the "emotional stimulus" induced a significant increase in NE excretion, but non-significant alterations in E excretion. Similar changes were noted in normotensive controls. In patients with cerebral hemorrhage, almost all hypertensive, and in hypertensive controls, ES brought about a consistent rise in E excretion without influencing significantly the NE excretion. The presence of a constant increase in E excretion after a mild emotion not only in patients with cerebral hemorrhage but also in subjects with uncomplicated essential hypertension, suggests that the E release found in patients with cerebral hemorrhage is related to the hypertensive state pre-existing the stroke rather than to hemorrhagic stroke itself. The pattern of catecholamine discharge in hypertensive patients might play a part in the occurrence of cerebral hemorrhagic accidents. The epinephrine discharges induce sudden increases in systolic blood pressure which could lead to the rupture of cerebral vessels with hyalinotic or atherosclerotic alterations.