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An invasive bivalve of the genus Mytilopsis has been present in the Indo-Pacific region since at least 1870, although most of the literature on this species states that it invaded the Pacific from the Caribbean through the Panama Canal after 1914. Although species of Mytilopsis are difficult to identify using morphological characters, difficult does not mean impossible. Comparisons of recently collected specimens as well as museum holdings suggest that the invasive Indo-Pacific bivalve is Mytilopsis adamsi, although further research including genetic analyses can help to answer this question. Review of literature and historical records support the interpretation that the invasive species of Mytilopsis in the Indo-Pacific probably originated in the eastern Pacific and not the Caribbean. If phylogenetic constructions within the family Dreissenidae have used genetic sequences from a misidentified species they must be revised.

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Introduction La maladie a IgG4 est une pathologie inflammatoire se manifestant par une hypertrophie d’un ou plusieurs organes associee a un infiltrat lymphoplasmocytaire produisant des IgG de type 4. L’atteinte hypophysaire est rare mais connue. Elle peut se reveler par un syndrome tumoral sellaire, des deficits hypophysaires isoles et/ou multiples et/ou un diabete insipide. Nous rapportons ici un nouveau cas d’hypophysite a IgG4 dont la presentation originale associait une nevralgie du V1-2 et paralysie du VI, sans deficit hormonal. Observation Une femme de 52 ans aux antecedents de maladie de Basedow, consulte pour nevralgie peri-orbitaire droite et hypoesthesie des territoires des branches V1 et V2, et paralysie du VI droits. L’IRM cerebrale montre une hypophyse globuleuse et heterogene, associee a un epaississement de la tige pituitaire et un aspect infiltre d’allure inflammatoire des sinus caverneux, predominant a droite. Le bilan hypophysaire retrouve une hyperprolactinemie de deconnection sans autre anomalie. Bilan sanguin sans anomalie. Anti-ANCA et IgG4 plasmatiques normales. Ponction lombaire montrant une hyperproteinorachie isolee et un ratio IL6/IL10 en faveur d’une pathologie inflammatoire. Biopsie des glandes salivaires normale. Le TEP scanner 18FDG retrouve une fixation hypophysaire intense sans autre atteinte. Le scanner TAP est normal. Une biopsie trans-sphenoidale de la lesion est realisee et l’analyse immunohistochimique confirme la presence d’un infiltrat lymphoplasmocytaire de type polyclonal exprimant des IgG4. Une corticotherapie IV sur 3 jours a permis l’amelioration des symptomes. Conclusion Presentation clinique inhabituelle d’une hypophysite a IgG4 avec tableau neurologique douloureux compressif caverneux droit sans deficit hypophysaire.

Charcot–Marie–Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22 . Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A. * Abbreviations : cAMP : cyclic adenosine monophosphate CMT1A : Charcot–Marie–Tooth disease type 1A

Introduction and Aims. This paper describes the sociodemographic characteristics of 196 psychotic patients admitted to acute psychiatric wards in the UK, Denmark, Germany and Italy, with the aim of comparing comorbid with non-comorbid patients. Design and Methods. It is a prospective field study with repeated measures at 1, 6 and 12 months. Patients were recruited from acute psychiatric wards in four European centres. They were grouped as comorbid or not on the basis of urine analysis. The Schedules for Clinical Assessment in Neuropsychiatry was used to provide a psychiatric diagnosis, and the Positive and Negative Symptom Severity Scale for further information on specific symptoms with results from the Fragerstrom test for nicotine dependence also reported. Results. Comorbid patients were younger than those who were not but did not differ significantly in the other sociodemographic measures. Differences in sociodemographic characteristics of patients between centres were apparent. Comorbid patients had higher levels of positive and lower levels of negative symptoms than those who were non-comorbid. Differences were found in the patterns of drug use between comorbid patients who were using cannabis compared with those who were not. Discussion and Conclusions. Cross-cultural differences in the sociodemographic characteristics of the comorbid patient population give us a better insight into this heterogenous group.[Baldacchino A, Blair H, Scherbaum N, Grosse-Vehne E, Riglietta M, Tidone L, Criaco C, Marelli MC, Sommer B, Tan L, Little H, Ghodse H. Drugs and Psychosis Project: A multi-centre European study on comorbidity. Drug Alcohol Rev 2009;28:379–389]

Successful intertidal mollusk farming requires a working knowledge of the biology, density, dynamics, and distribution of mollusk populations. Little Skookum Shellfish Growers (LSSG) has operated under economically and environmentally sustainable sea ranching guidelines for Manila clams (Venerupis philippinarum) since 1977 in Little Skookum Inlet near Shelton, Washington, USA. LSSG's system of benthic surveys and seeding offers a rational approach for establishing and monitoring standing stocks and biomass dynamics of infaunal mollusk populations, allowing LSSG to sea ranch Manila clams in excess of 60,000 kg/ha/y in sustainable yield. Until successful acoustical methods for infaunal biomass analysis are established, this approach may be the only cost effective way of achieving economical and sustainable results with a full working knowledge of the impacts involved in either intertidal sea ranching or stock enhancement for infaunal mollusks.

The tropical Asian green mussel, Perna viridis (Bivalvia: Mytilidae) is a recent invader in the Caribbean Basin, including the subtropical southeastern United States. In this study we examined the (1) range of P. viridis in the southeastern United States, (2) relative abundance of P. viridis across habitats and (3) density of P. viridis in Tampa Bay, FL. The invasion and spread of P. viridis in the southeastern United States was estimated by a combination of first-hand qualitative sampling and second-hand observations. There were apparently at least two discrete introductions, each followed by natural dispersal. The initial invasion was discovered in Tampa Bay in 1999, and was followed by rapid spread of P. viridis south as far as Marco Island, FL, but limited spread northward. In 2002, a second invasion occurred in northeast Florida, separated from the west Florida population by 650 km of coastline. On the east coast, P. viridis appeared to be distributed discontinuously between South Carolina a...

Bay scallops (Argopecten irradians [Lamarck]) are a culturally and economically important component of Florida's nearshore marine community. However, many of the local populations that compose the bay scallop metapopulation in Florida have virtually disappeared since the 1950s. This study reports the results of a 3-year effort to restore bay scallop populations at 4 sites along the west central coast of the state (Tampa Bay, Anclote, Homosassa and Crystal River). During late summer of 1997, 1998 and 1999, wild adult scallops were retrieved from each of those four target sites and induced to spawn in the laboratory. The resultant offspring were grown to at least 20-mm shell height in a nursery setting and then transplanted to cages deployed at the site where their parents were originally harvested. The growth, survival and reproductive development of the planted scallops were recorded on an approximate 6-week schedule. Results suggest that caged scallops generally grew more slowly than their wild ...

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclero therapy ; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclero therapy ; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occur rence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. "Standard," low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.

ObjectiveThe objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).DesignRandomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.MethodsSixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20–40 mg once daily and hydrocortisone 20–40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).ResultsIn stage 1, patients had a median 1.5 (range, 1–9) intercurrent illness events with DR-HC and 1.0 (1–8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1–3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.ConclusionsThis long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

Genetically conservative changes in a bivalve population may be mirrored by morphological changes in the shells of individuals in that population. The rate of such evolutionary change is usually so slow that the changes in shell morphology cannot be detected in short-term studies of local populations. When selective pressure becomes severe, however, the magnitude of the genetic changes may be intensified, and thus the magnitude of the morphological changes in the shells may be greater—and more detectable. We compared the morphometric features of specimens from archaeological sites with those from geographically coherent modern collections to determine if such detectable morphological changes have taken place in the populations studied. Analyses of bay scallop shells (Argopecten irradians) from nine modern populations spanning Florida's entire Gulf coast and from four archaeological sites located from central to southern Florida reveal that major morphological shifts in the shells of two local populations have occurred sometime in the past 500 to 1500 years. These shifts may have implications regarding the persistence of the scallop metapopulations and the efficacy of future efforts to conserve the species.

Conventional wisdom suggests that pelagically borne marine invertebrate larvae are &Spersed considerable distances from their source population, but recent research provides evldence that at least in some instances larvae may be retained within the local environment. From June 1995 through June 1996, we monitored adult abundance and juvenile recruitment in 4 geographically separated bay scallop Argopecten irradjans populations occurring along the Gulf of Mexico coast of Florida, USA. Populations at our Anclote and Homosassa study sites had low adult abundances (generally 25 scallops per 600 m? survey transect) during those years. Similarly, recruitment to art~ficial spat collectors was a rare event at Anclote and Homosassa, where we typically collected fewer than 0.1 scallops per collector per day. In contrast, recruits were common at Steinhatchee and St. Joseph Bay, where daily recruitment rates exceeded those observed at Anclote and Homosassa by 1.5 to 2 orders of magnitude. Whereas differences in adult abundance and juvenile recruitment were pronounced among sites, differences among stations within each site were minor and generally not significant. Based upon these observations and knowledge of the distribution and abundance of bay scallops in Floridan Gulf of Mexico waters, our results suggest that during 1995-96, dispersal of bay scallop larvae was widespread within each study site but that transport of larvae away from the adult habitat was uncommon and ultimately unsuccessful. We discuss oceanographic features that may support local retention of bay scallop larvae along the west coast of Florida, and we suggest that periodic interruptions of those oceanographic processes may explain the previously reported genetic homogeneity among bay scallop populations in Florida.

Shell growth rate is an important component of fitness in bivalve molluscs. Using the ω parameter computed from the von Bertalanffy growth equation, we quantitatively compared rates of annual shell grwoth among the hard clams Mercenaria mercenaria, M. campechiensis, and their hybrids sampled from a variety of habitats in the Indian River lagoon, Florida, USA, a zone of species overlap and natural hybridization. Our results indicate that the classical paradigm describing hard clam growth, in which growth rate is fastest in M. campechiensis, intermediate in hybrids, and slowest in M. mercenaria is not supported in the Indian River lagoon. Instead, M. campechiensis has a growth advantage in deep-water habitats in the northern section of our study area. In the central and southern sections of our study area, hybrids have a growth advantage over M. mercenaria in shallow-water habitats, but M. mercenaria has a growth advantage over hybrids in deep-water habitats. In all other sampled habitats, either growth rate among genotype classes is equal, or M. mercenaria has a growth advantage. This complex relationship between genotype and habitat-specific growth provides a mechanism for selection to act on hard clams in the Indian River.

The etiology of bivalve gonadal neoplasia has eluded invertebrate pathologists for over 20 yr. In a coastal Florida (USA) lagoon, where two species of hard clams (Mercenaria mercenaria and M. campechiensis) cooccur and hybridize, they exhibit a persistent, unusually high frequency of gonadal neoplasia. Hybridity, rather than environmental or other biological factors, appears to determine susceptibility, implicating a genetic mechanism in the etiology of the disease. However, the increase in frequency of occurrence of the disease in hybrids is not accompanied by an increase in severity beyond that experienced by pure-species genotypes, suggesting that only some components of the genetic mechanism are affected by hybridization. Differences between sexes in the overall and size-specific frequency of occurrence and in severity of the disease suggest that the genetic mechanism is associated with sex. The excessive susceptibility of hybrid genotypes to gonadal neoplasia results in reduced hybrid fitness and constitutes an unambiguous example of a cellular disease that acts as a barrier to gene flow between species. Moreover, because these species are of commercial importance, fishery practices that promote hybridization are common and, over time, may reduce the fitness of natural populations.

This paper describes the sociodemographic characteristics of 196 psychotic patients admitted to acute psychiatric wards in the UK, Denmark, Germany and Italy, with the aim of comparing comorbid with non-comorbid patients.It is a prospective field study with repeated measures at 1, 6 and 12 months. Patients were recruited from acute psychiatric wards in four European centres. They were grouped as comorbid or not on the basis of urine analysis. The Schedules for Clinical Assessment in Neuropsychiatry was used to provide a psychiatric diagnosis, and the Positive and Negative Symptom Severity Scale for further information on specific symptoms with results from the Fragerstrom test for nicotine dependence also reported.Comorbid patients were younger than those who were not but did not differ significantly in the other sociodemographic measures. Differences in sociodemographic characteristics of patients between centres were apparent. Comorbid patients had higher levels of positive and lower levels of negative symptoms than those who were non-comorbid. Differences were found in the patterns of drug use between comorbid patients who were using cannabis compared with those who were not.Cross-cultural differences in the sociodemographic characteristics of the comorbid patient population give us a better insight into this heterogenous group.

Microgeographic variation in shell growth rate of Mercenaria mercenaria (L.) among habitats within the Indian River, Florida, was studied to develop a baseline against which the significance of M. mercenaria shell growth rate differences observed over a larger geographic scale could be compared. Hard clams of the genus Mercenaria were collected from 525 randomly located stations within the Indian River during July and August, 1986. Clams ( n = 922) were returned to the laboratory and taxonomically identified using diagnostic protein loci. Clams identified as M. mercenaria ( n = 465) were isolated and their shell growth rate determined by internal shell growth-increment analysis. The annual pattern of internal shell growth-increment formation in genetically identified M. mercenaria from the Indian River was documented using specimens collected monthly from September 1987 through August 1988. The translucent (slow growth) increment was deposited during summer and fall, whereas the remainder of the year was characterized by formation of the opaque (rapid growth) increment. This pattern is similar to that described for other hard clam populations from the southeastern United States. To compare shell growth rates of M. mercenaria among habitats within the Indian River, we used the ω parameter of Gallucci and Quinn. The range of variation in ω among habitats within the Indian River was similar to that observed for hard clams in Narragansett Bay, Rhode Island, but less than that observed for hard clams from various sites throughout the state of Florida. Shell growth rates of M. mercenaria in the Indian River increased with decreasing depth, and shell growth rates were more rapid in areas characterized by the presence of submerged aquatic vegetation than in areas devoid of such vegetation. Results of this study indicate that comparisons of shell growth rates among hard clam populations over a wide geographic range must be tempered by a consideration of shell growth rate variation among habitats within each site.

Long porphyrin molecular wires presenting optical transparency and light diffraction are fabricated and characterized using optical and atomic force microscopy. The development of dual photonic/electronic self-assembled devices is discussed.

ATPase activity was investigated in sciatic and optic nerves of female mutant diabetic C57Bl/Ks (db/db) mice and age-matched control mice (db/m and m/m). Nerves from animals aged 50, 70, 125, 180 and 280 days were assayed in vitro for ATPase activity in the presence or absence of ouabain: the ouabain-sensitive fraction contained Na+,K(+)-ATPase. Enzymatic activity was compared within and between age-matched groups. No significant difference in Na+,K(+)-ATPase activity was detected between the diabetic and control mice, whether expressed as mumol Pi/h-1 formed per gramme wet weight or per nerve (protein content). The activity decreased by about 25% in both the sciatic and optic nerves of the oldest animals. These results were strikingly similar in all groups, regardless of the type of nerve examined, confirming that the development of neuropathy in this animal model is unrelated to the postulated derangement of Na+,K(+)-ATPase activity. Among possible explanations, a lack of polyol pathway activation was investigated by staining the sciatic nerves of animals from all groups with the peroxidase-antiperoxidase procedure using a polyclonal antiserum raised against the enzyme aldose reductase. Histological sections of all nerves were consistently negative, suggesting that these animals actually lack the enzyme involved in activating the self-perpetuating metabolic cycle leading to deranged nerve function. The db/db mouse appears to present particular biochemical changes which merit attention with a view to clarifying the pathogenesis of diabetic neuropathy.

Comparison of 18S ribosomal RNA gene sequences between diverse bivalve species, including eight scallop species, allowed the design of an 18S rRNA targeted oligonucleotide probe (BS-1364) that was specific for scallops belonging to the genus Argopecten (bay and calico scallops). The high sequence similarity of the 18S rRNA gene between Argopecten irradians and Argopecten gibbus (98.8%) prevented the design of an A. irradians species-specific probe. Hybridization studies using amplified 18S rDNA from a diverse collection of bivalve species demonstrated that the specificity of the digoxygenin-labeled probe was consistent with the predicted specificity indicated by sequence comparison. Hybridization studies using laboratory-spawned bay scallop veligers indicated that a single veliger could be detected by probe hybridization in a blot format, and that probe hybridization signal was proportional (r(2) =.99) to the abundance of veligers. Methods for rRNA extraction and blotting were developed that allowed bay scallop veligers to be specifically and quantitatively identified in natural plankton samples. Preliminary studies conducted in Tampa Bay, Florida, suggest that introduced scallops can successfully spawn and produce veligers under in situ conditions. The Argopecten-specific probe and methods developed in this study provide the means to study the production and fate of bay scallop larvae in nature and provide evidence that scallops introduced into Tampa Bay have the potential for successful reproduction and enhancement of scallop stocks.

The present study was undertaken in order to evaluate the efficacy of the intravenous administration of Albunex in obtaining left ventricular opacification and the relationship between left ventricular opacification and pulmonary pressures and cardiac function.Fifty-two adult patients, mostly affected by ischemic heart disease, were enrolled in the study. In 37 of these patients, a complete right heart hemodynamic study was performed after Swan-Ganz catheterization. Albunex was administered in three randomized doses (0.10, 0.15 and 0.20 ml/kg) to all the patients. Left ventricular opacification was assessed both visually and using videodensitometric analysis.Left ventricular opacification was obtained in 93% of all the injections and an intermediate or strong opacification was obtained in 68%, while absent opacification was observed in 6% of the injections, irrespective of the contrast dose. An incremental opacification efficacy trend was observed from the lower to the higher dose, with an intermediate or strong opacification in 58 and in 77% of 0.10 and 0.20 ml/kg injections, respectively. Irrespective of the contrast dose, an enhancement of the endocardial borders was observed in 61% of the wall segments suboptimally visualized in basal conditions. The endocardial borders enhancement was obtained in 39 and in 79% of segments using the 0.10 and the 0.20 ml/kg doses, respectively. No statistically significant differences were observed between the videodensitometric parameters obtained using the three contrast doses. Finally, a significant relationship was observed between left ventricular opacification parameters and pulmonary pressures and left ventricular functional parameters, irrespective of the contrast doses considered.The results we obtained demonstrate the good overall efficacy of Albunex administered intravenously in order to obtain left ventricular opacification in a clinical population of cardiac patients. Moreover, they suggest that the dosage to be used clinically should preferably be at least 0.20 ml/kg, although no significant influence of contrast dosage on videodensitometric parameters has been observed. Finally, irrespective of the contrast dosage, the magnitude of left ventricular opacification appears to be influenced by the hemodynamic status of the patient.

Background and hypothesis: Myocardial contrast echocardiography using second‐generation agents has been proposed to study myocardial perfusion. A placebo‐controlled, multi‐center trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second‐generation echo contrast agent, and to compare this technique with technetium ‐ 99m sestamibi (MIBI) single‐photon emission computed tomography (SPECT). Methods: In a placebo‐controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram‐ (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 μl particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 μl particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. Results: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p=0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61–80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66–81% and a high specificity (80–96%), but in low sensitivity (20–39%) of MCE for the detection of perfusion defects. Conclusion: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 μl particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.

Leucoencephalopathy with intracranial calcifications and cysts (LCC) is a rare disorder of unknown origin characterised radiologically by white matter abnormalities, calcifications and cysts with contrast enhancing nodules.1–4 Neuropathology reveals “angiomatous-like” rearrangements of microvessels and Rosenthal fibres (RF).1–3 The onset is almost invariably in early infancy to adolescence. Occurrence of disease in siblings suggests autosomal recessive inheritance.2 3 Neurological manifestations include cognitive decline, seizures, obstructive hydrocephalus, and progressive cerebellar, extrapyramidal and pyramidal signs. As some patients have visual disturbances and retinal vascular abnormalities resembling Coats’ disease,2 LCC has been linked to Coats plus syndrome, a rare disease characterised by retinal vascular abnormalities, leucoencephalopathy and calcifications without brain cysts.2 5 Systemic involvement is common with haematological, enteric, dermatological or skeletal abnormalities.2 5 We describe two sporadic patients with late onset LCC. ### Patient No 1 A 27-year-old woman, born to healthy non-consanguineous parents, presented with 5 month progression of symptoms of intracranial hypertension. Brain MRI showed the following: a large left thalamic cyst compressing the aqueduct and the third ventricle with triventricular hydrocephalus; another cerebellar cyst with a rim of post contrast enhancement; supratentorial and left cerebellar white matter hyperintensities on T2 weighted images; and post contrast enhancing nodules in the basal ganglia, thalami and centra semiovalia, densely calcified at CT (fig 1). Spinal …

This trial evaluated whether the intravenous injection of an ultrasound contrast agent (Infoson) facilitates the assessment of systolic function in 40 low-echogenic patients undergoing low-dose (4 mcg/kg/min) dopamine echocardiography. Interobserver difference in calculated ejection fraction at entry was10%. Echocardiographic monitoring was performed in the apical 4-chamber view at four intervals: baseline, no contrast; first Infoson injection; dopamine infusion, no contrast; dopamine infusion+second Infoson injection. The left ventricle was divided into 5 segments and analysis was performed by two blinded observers. Wall motion abnormalities, ejection fraction and the confidence in detecting the endocardial border, were assessed. Infoson provided adequate left ventricular opacification in 90% of the injections, with a significant improvement in endocardial border detection. The interobserver variability of ejection fraction measurements was significantly reduced. The probability of attaining concordance between the investigators on wall motion assessment improved significantly. These results suggest potential applications in stress echocardiography.

Between January and December 1992 an epidemiological survey on the risk factors for cardiovascular disease in eighteen-year old boys during call-up has been performed in Verona. The study involved 3426 subjects: 100% of the boys coming from the metropolitan area and 65% of those coming from the non-metropolitan areas. A family history of hypertension was found in 9.54% of the subjects and a family history of myocardial infarction or sudden death was found in 4.54% of the subjects. 0.18% of the population reported diabetes and 2% hypertension. Prevalence of smoke addiction was 39.1% and in this group 17.54% smokedor = 20 cigarettes/day. Prevalence of smoke addiction was significantly greater in the boys having one or both smoking parents (p0.001), in working people in respect to students (p0.001), in boys from metropolitan in respect to those from non-metropolitan areas (p = 0.033), and among those not practising sport activity (p0.001). Mean systolic and diastolic blood pressure were 130.16 +/- 13/74.48 +/- 9 mm Hg and 90th percentile was 149/87 mm Hg. Systolic and diastolic blood pressure were significantly lower in boys from metropolitan in respect to those from non-metropolitan areas and in smokers in respect to non smokers. A body mass indexor = 30 was found in 3.04% of the subjects, the body mass index being directly related to systolic and diastolic blood pressure (p0.001). Total cholesterol performed on a voluntary basis from capillary blood samples by Reflotron System was determined in 80.06% of the subjects. Mean blood cholesterol was 139.1 +/- 28 mg/dL and 90th percentile's value was 182 mg/dL. Mean blood cholesterol was significantly lower in non-metropolitan in respect to metropolitan areas (p = 0.033). 44.48% of the subjects had one or more risk factors, 5.22% had two risk factors and 0.67% three or more risk factors for cardiovascular disease. This study shows that 1) in this population of young people a significant part is exposed to one or more cardiovascular risk factors; 2) social and environmental factors affect, sometimes deeply, the prevalence of cardiovascular risk factors; 3) The visit for call-up appears to be important in the setting-up of a strategy of primary prevention for cardiovascular disease.

This randomized double-blind comparative study was designed to investigate the safety and efficacy of a new nonionic monomeric contrast agent, Iopentol 350 mgI/ml, versus a nonionic monomeric contrast agent currently used, Iopamidol 370 mgI/ml, in cardioangiography. Blood pressure, heart rate, end-diastolic left ventricular and mean aortic pressure, ECG, adverse reactions and discomfort were the safety variables recorded; technical adequacy and diagnostic yield were the efficacy variables recorded. A hundred patients entered the trial and were subdivided into two groups of 50 patients each; all of them were included in the safety and efficacy assessments. Demographic data, general and background characteristics and procedural data were comparable in the two treatment groups. No significant difference in efficacy was observed between the two groups: diagnostic yield was optimal in 90% of the patients in the Iopentol group and in 88% of the patients in the Iopamidol group. Systolic blood pressure 30 min. after the examination showed, in both groups, a slight but statistically significant reduction relative to baseline values (-3.48 mmHg and -3.85 mmHg in the Iopentol and in the Iopamidol group, respectively), while no significant reduction was observed in diastolic blood pressure. A statistically but not clinically significant decrease in heart rate was observed in the Iopamidol group 30 min. after the examination (-5.05%), while this variable remained practically the same in the Iopentol group (-0.58%). No difference was found between the two groups relative to the incidence of discomfort following the injection. Other adverse reactions were experienced by 7 patients in the Iopentol group and by 9 patients in the Iopamidol group: they all promptly recovered after medical treatment, with no sequelae. All but one event in the Iopamidol group (chest and abdominal pain with ECG changes) were mild to moderate and mainly related to the procedure and to the underlying disease. In conclusion, both contrast agents are safe and effective for use in cardioangiography.

In 87 patients with chronic venous hypertensive microangiopathy the efficacy of oral FTTCA (Centella asiatica) administered for 60 days was tested. The microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo was assessed in a double blind study. The compound was well tolerated and no unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the abnormally increased RF, PCO2 decreased and PO2 increased in comparison with values measured at inclusion. These results confirm the efficacy of FTTCA in venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to be dose-related.

The acute variation in capillary filtration [CF] was evaluated with strain-gauge plethysmography in patients with severe venous hypertension due to deep venous disease. Two groups were selected and randomly treated with a single oral dose or TTFCA (60 mg or 120 mg). CF was assessed again after 5 and 10 hours. Eleven patients were randomised in the 60 mg group and 9 in the 120 mg group. Also 5 normal subjects were studied with the same procedure to act as controls. No variations in CF were observed in normal limbs. In both groups of patients there was a significant decrease in CF after 5 and 10 hours. The percent decrease in CF after 10 hours was higher in the high dose group. These results indicate that TTFCA is acutely effective in reducing CF and oedema in subjects with venous hypertensive microangiopathy. The effects of TTFCA on CF appear to be dose related.

High arteriolar resistance and vasoconstriction are considered an important factor in essential hypertension. In 98 patients with essential hypertension and 60 normals we evaluated skin flow at rest (RF) and the veno-arteriolar response (VAR = the vasoconstriction due to leg dependency) using laser-Doppler flowmetry. Measurements were repeated after four weeks in normals and after treatment with nifedipine (10 mg tid) in hypertensives. At the beginning of the study in hypertensives RF and VAR were lower than in normals. After nifedipine treatment a decrease in blood pressure was associated with an increase in RF and VAR. A difference was also observed between responders and non responders (16.3%). RF and VAR at the beginning of the study were both higher in non responders and did not change after treatment indicating that the degree of vasoconstriction in these patients was lower. In conclusion microcirculation changes in hypertension may be quantified by laser-Doppler flowmetry and used to evaluate vasoconstriction and the effects of drugs.

In subjects with lymphatic problems and postphlebitic edema there is a significant difference in the ratio between lymphatic and plasma concentration of protein (CL/CP) in the foot. Two groups of patients were studied (one group with lymphedema and the other with postphlebitic limbs) in order to assess the CL/CP ratio before and after TTCFA treatment (Centellase). The study confirmed the efficacy of treatment in achieving a significant reduction of CL/CP and distal edema.

In an open-study design five healthy volunteers were first given 2500 IU sodium heparin intravenously and then, after 72 h, another injection of the same dosage of sodium heparin followed immediately by 400 mg defibrotide intravenously. In two separate experiments, prothrombin time, activated partial prothrombin time, antithrombin III, tissue plasminogen activator, its inhibitor and plasma heparin levels were measured at baseline and after 15 min in one experiment, and at baseline and after 2 h in the other experiment. The most important finding was that an interaction exists between heparin and defibrotide on haemostatic activity: activated partial prothrombin time was increased three-fold in volunteers given the defibrotide—heparin combination compared with volunteers given heparin alone. This statistically and clinically significant effect was evident 15 min after administration of defibrotide–heparin and was still present after 2 h. Possible explanations for this effect are discussed briefly.

The value of elastic compression and defibrotide, a profibrinolytic and antithrombotic drug, in patients with venous hypertension, lipodermatosclerosis and ulceration was assessed in a cross-over trial. Elastic compression alone and in association with defibrotide (800 mg/day) were completed the study (18 were treated with the combined treatment in the first 3 months and 14 in the second period). We evaluated the decrease of the areas of liposclerosis and ulceration by computerized analysis of the areas. We also studied the decrease of leg circumference and subjective clinical improvement by an analogue scale line. Patients were also evaluated by laser-Doppler flowimetry, transcutaneous PO2 and PCO2 measurements, capillary permeability and fibrinolytic activity. Both forms of treatment were active in reducing the areas of liposclerosis and ulceration but combined treatment with defibrotide and elastic compression was significantly more effective in reducing both liposclerosis and ulceration, and in improving microcirculatory parameters and capillary permeability. The improvement in objective evaluation was comparable to the clinical improvement measured by the analogue score. The positive variation of all parameters studied was associated with a significant increase of fibrinolytic activity during the administration of defibrotide. No side effects were observed during this study. These results suggest that defibrotide treatment is effective in treating liposclerosis and ulceration in postphlebitic limbs with venous hypertension, improving both microcirculatory parameters and subjective symptoms.

The evaluation of the effects of elastic compression in patients with venous hypertension and perimalleolar ulceration may be performed using laser-Doppler flowmetry (LDF). This technique may reveal microcirculatory positive variations which are not evident by standard methods as Doppler, plethysmography and ambulatory venous pressure (AVP). In this study we demonstrated the good correlation between AVP values and laser-Doppler parameters, particularly the resting flow and the venous vasomotor response. Also the response of the skin of the perimalleolar region to a local increase of skin temperature was well correlated with AVP parameters. By evaluation of laser-Doppler parameters it was possible to differentiate normals from abnormals (patients with venous hypertension) and it was possible to show variations of microcirculation associated with the decrease of the areas of ulceration after 3 week elastic compression. No significant variations have been recorded by AVP before and after 3 weeks of treatment with elastic compression in 80 patients with venous ulcerations. Laser-Doppler flowmetry was useful to evaluate the positive changes produced by elastic compression.

CAPD provides a viable alternative to hemodialysis for ESRD, because of the serum chemistry and clinic results obtained and the independence and quality of life that patients can achieve. Nineteen patients treated by CAPD for an average of 19.4 mo demonstrate the adequacy of this treatment.