Prognostic role and interaction of TERT promoter status, telomere length and MGMT promoter methylation in newly diagnosed IDH wild-type glioblastoma patients.

BACKGROUND: The clinical relevance of promoter mutations and single nucleotide polymorphism rs2853669 of telomerase reverse transcriptase (TERT) and telomere length in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients remains unclear. Moreover, some studies speculated that TERT promoter status might influence the prognostic role of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in newly diagnosed GBM. We carried out a large study to investigate their clinical impact and their interaction in newly diagnosed GBM patients. PATIENTS AND METHODS: We included 273 newly diagnosed IDH wild-type GBM patients who started treatment at Veneto Institute of Oncology IOV - IRCCS (Padua, Italy) from December 2016 to January 2020. TERT promoter mutations (-124 C>T and -146 C>T) and SNP rs2853669 (-245 T>C), relative telomere length (RTL) and MGMT methylation status were retrospectively assessed in this prospective cohort of patients. RESULTS: Median overall survival (OS) of 273 newly diagnosed IDH wild-type GBM patients was 15 months. TERT promoter was mutated in 80.2% of patients, and most had the rs2853669 single nucleotide polymorphism as T/T genotype (46.2%). Median RTL was 1.57 (interquartile range 1.13-2.32). MGMT promoter was methylated in 53.4% of cases. At multivariable analysis, RTL and TERT promoter mutations were not associated with OS or progression-free survival (PFS). Notably, patients C carrier of rs2853669 (C/C+C/T genotypes) showed a better PFS compared with those with the T/T genotype (hazard ratio 0.69, P = 0.007). In terms of OS and PFS, all interactions between MGMT, TERT and RTL and between TERT and rs2853669 genotype were not statistically significant. CONCLUSIONS: Our findings suggest the presence of the C variant allele at the rs2853669 of the TERT promoter as an attractive independent prognostic biomarker of disease progression in IDH wild-type GBM patients. RTL and TERT promoter mutational status were not correlated to survival regardless of MGMT methylation status.

Author Correction: Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.

Correction to: Eur Rev Med Pharmacol Sci 2021; 25 (19): 5889-5903. DOI: 10.26355/eurrev_202110_26865. PMID: 34661247-published online on October 12, 2021. In the main text, D-dimer unit of measurement was mistakenly indicated as mg/dL rather than as ng/mL. The sentence "With regard to markers of coagulation, non-survivors showed significantly higher median levels of D-dimer as compared to survivors: 1348 mg/dL 949.5 mg/dL, respectively (p=0.03)." in its correct form is the following: "With regard to markers of coagulation, non-survivors showed significantly higher median levels of D-dimer as compared to survivors: 1348 ng/mL vs. 949.5 ng/mL, respectively (p=0.03).". In the first column of Table III (third row), D-dimer unit of measurement was mistakenly indicated as mg/dL rather than as ng/mL. Correction: "D-dimer (ng/mL)". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/26865.

Chilblain-like lesions (COVID-19 toes) have the same impact on family members than psoriasis systemically treated: insights from a case-control study targeting the pediatric population.

OBJECTIVE: COVID-19 toes represent the main dermatological COVID-19 cutaneous manifestation in pediatric patients. Its diagnosis exposes the whole family to social stigma and this aspect was not previously evaluated. PATIENTS AND METHODS: This was a multicenter, case-control, observational study that compared the family impact of COVID-19 toes vs. psoriasis (PsO). We enrolled 46 pediatric patients (23 with psoriasis and 23 with COVID-19 toes, age and gender matched) and their parents/caregivers that had to fill the Dermatitis Family Impact (DFI) questionnaire. RESULTS: DFI index did not differ significantly between both subgroups (p=0.48), and in psoriatic patients did not correlate with both Psoriasis Area Severity Index (PASI) (p=0.59) and itch-VAS (p=0.16). CONCLUSIONS: COVID-19 toes, a transitory dermatosis, exerted a similar impact/perturbation on family dynamics than PsO, a well-known stigmatizing, chronic inflammatory dermatosis.

Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.

Relationship between proinflammatory cytokines (Il-1beta, Il-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer's disease.

Inflammation plays a crucial role in Alzheimer's disease (AD). AD neurodegeneration and concurrent involvement of the peripheral immune system may promote leukocyte division and telomere shortening. We examined genotypes and plasma levels of two proinflammatory cytokines, IL-1beta and IL-18, and leukocyte telomere length (LTL) in patients with mild cognitive impairment (MCI) and AD. We wanted to determine whether changes in plasma IL-1beta and IL-18 levels, together with LTL shortening, could be diagnostic for disease progression from MCI to AD. Median plasma IL-1beta levels were in the order MCI patients (2.2 pg/ml) < AD patients (4.0 pg/ml), both of which differed significantly from the controls (0.0 pg/ml). In the AD patients, the lowest IL-1beta levels were associated with the presence of the C allele of IL-1beta rs16944 SNP. Median plasma IL-18 levels were in the order MCI patients (116.3 pg/ml) > AD patients (85.8 pg/ml), both of which were significantly higher than in the controls (17.6 pg/ml). Analysis of LTL showed a progressive reduction in the order controls > MCI > AD patients (p < 0.0001). Overall LTL reduction was correlated with increased plasma IL-1beta levels, substantiating the hypothesis that inflammatory processes secondary to neuroinflammation may trigger telomere attrition. Changes in plasma IL-1beta and Il-18 levels, and LTL seem to reflect shifts in AD stage; they may have potential use as blood biomarkers to monitor disease onset and progression from MCI to AD.

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81µgcm-2h-1 whereas the highest iontophoretic transport was 46.4±3.6µgcm-2h-1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.

Effects of NaCl stress on seed germination and seedling development of Brassica insularis Moris (Brassicaceae).

Brassica insularis is a protected plant that grows on both coastal and inland cliffs in the western Mediterranean Basin. The objective of this study was to test if any variability exists in the salt stress response during seed germination and seedling development in this species relative to its provenance habitat. Variability among three populations in the salt stress effects on seed germination and recovery under different temperatures was evaluated. The effect of nebulisation of a salt solution on seedling development was evaluated between populations growing at different distances from the sea. Seeds of B. insularis could germinate at NaCl concentrations up to 200 mm. Seed viability was negatively affected by salt, and recovery ability decreased with increasing temperature or salinity. Inter-population variability was detected in salt response during the seed germination phase, as well as in seedling salt spray tolerance. The inland population seedlings had drastically decreased survival and life span and failed to survive to the end of the experiment. In contrast, at least 90% of the coastal seedlings survived, even when sprayed at the highest frequency with salt solution. This study allowed investigation of two natural factors, soil salinity and marine aerosols, widely present in the B. insularis habitat, and provided the first insights into ecology of this protected species and its distribution in the Mediterranean. These results might be useful in understanding the actual distributions of other species with the same ecology that experience these same abiotic parameters.

El proceso de cuidar a la familia en urgencias. Una aproximación desde la teoría fundamentada / The process of family care in the emergency unit: an approach from grounded theory

OBJETIVOS: analizar la percepción que tienen los profesionales enfermeros respecto al acompañamiento familiar en un servicio de urgencias, así como identificar los cuidados que proporcionan a las familias que viven situaciones de final de vida. MÉTODO: se utilizó la teoría fundamentada (Grounded Theory) como método de investigación cualitativa. La población de estudio fueron enfermeras y enfermeros que trabajaban en urgencias generales de adultos. El número de participantes se determinó mediante muestreo teórico paralelo al transcurso de las entrevistas y análisis. Los instrumentos de recogida de información fueron el cuestionario de variables sociodemográficas y las entrevistas en profundidad semiestructuradas. La recogida de datos finalizó cuando hubo redundancia de información y las categorías se saturaron teóricamente. Dichos datos fueron tratados teniendo en cuenta la Ley Orgánica 15/1999, de 13 de diciembre, de protección de datos de carácter personal. Para buscar, seleccionar y organizar los datos, se utilizó el programa Weft-QDA. RESULTADOS: la experiencia del profesional mejora el cuidado a la familia, aunque la presión asistencial repercute negativamente en poder satisfacer sus necesidades. La información es un elemento terapéutico que favorece la comunicación entre la familia y el profesional. El vínculo establecido entre familia y profesional durante el proceso de morir fomenta un cuidado más humanizado. CONCLUSIÓN: las enfermeras/os quieren incluir a la familia en sus competencias asistenciales, abordándola holísticamente dentro del contexto del cuidado humanizado. Todavía quedan aspectos de la atención que son mejorables, como la calidad de información, los cambios organizativos y estructurales del servicio y el abordaje familiar en situaciones trágicas, inesperadas y traumáticas

OBJECTIVES: to analyze the perception by nursing professionals of family accompaniment in an Emergency Unit, as well as to analyze the care provided to families facing end-of-life situations. METHOD: grounded Theory was used as a method for qualitative research. The study population consisted of male and female nurses working in the General Emergency Unit for adults. The number of participants was determined through theoretical sampling parallel to the course of interviews and analysis. The tools for data collection were the questionnaire of sociodemographical variables, and in-depth semi-structured interviews. Data collection ended when there was redundant information, and categories were theoretically saturated. Said data were treated according to Organic Law 15/1999 of December, 13th, on Personal Data Protection. The Weft-QDA program was used for data search, selection and organization. RESULTS: the experience of the professional will improve the care for the family, though high workload has a negative impact on the ability to meet their needs. Information is a therapeutic element that will encourage communication between the family and the professional. The link established between family and professional during the death process will favour a more human care. CONCLUSION: nurses want to include the family within their care responsibilities, with a holistic approach in the context of humanized care. There is still room for improvement in some aspects of care, such as the quality of information, organization and structural changes in the unit, and the approach to relatives in tragic, unexpected and traumatic situations

[Negative pressure system in the treatment of enterocutaneous fistulas in the pediatric population]. / Sistema de presión negativa en el tratamiento de fístulas enterocutáneas en la población pediátrica.

AIM OF THE STUDY: The management of children with enterocutaneous fistulas (EF) along with large abdominal wall defects secondary to multiple surgical interventions can be difficult and sometimes lead to intestinal failure (IF). The aim of this study is to present the results of negative pressure systems and their properties (edema reduction angiogenesis promotion and granulation tissue formation) in children with enterocutaneous fistulas (EF) and their prognosis. MATERIALS AND METHODS: A retrospective analysis of children with refractory, high output EF treated with NPS between 2008-2014. Outcome variables were duration and effectiveness of treatment as well as complications associated with NPS. RESULTS: Eight patients met inclusion criteria and were treated with NPS during a median of 25 days (range 5-50). The aetiologies were volvulus (2), necrotizing enterocolitis (2), gastroschisis (2), Blue Rubber Bleb Nevus (1) and duodenopancreatic anastomosis fistula following hepatopancreatic transplantation (1). Most patients (n=7) had large abdominal wall defects that closed during treatment, though two patients required further laparotomies due to evisceration. Two patients developed a second EF that was also successfully treated with NPS. No complications were identified arising from the use of NPS. After a 5-yr follow up 3 patients had a multivisceral transplantation and survive, and 4 died due to encephalopathy (1), hemolytic anemia (1), catheter-related sepsis (1) and one while waiting for a multivisceral graft for transplantation. CONCLUSIONS: Despite of a limited series of patients we recommend NPS as a useful tool in the management of EF and/ or abdominal wall defects.

OBJETIVOS: Las fístulas enterocutáneas (FE) de evolución tórpida y los defectos de pared abdominal (DPA) en niños multioperados son difíciles de manejar y pueden ser causa de fallo intestinal. El objetivo de este estudio fue analizar si el sistema de presión negativa (SPN) que disminuye el edema, favorece la vascularización y la aparición del tejido de granulación, mejora la cicatrización y el pronóstico de las FE. METODOS: Se realizó un estudio retrospectivo de niños multioperados con fístulas enterocutáneas recalcitrantes y de alto débito con o sin defectos de pared abdominal, entre 2008-2014 tratados con SPN. Las variables analizadas fueron el cierre de la fístula y/o defecto abdominal, el tiempo transcurrido y las complicaciones del tratamiento. RESULTADOS: Ocho pacientes cumplieron criterios de inclusión y fueron tratados con SPN con una mediana de 25 días (5-50). La etiología fue vólvulo intestinal (2), enterocolitis necrosante (2), gastrosquisis (2), Blue Rubber Bled Nevus (1) y fístula de anastomosis duodenopancreática en un trasplante hepatopancreático (1). Siete pacientes asociaron defectos de pared abdominal. Dos pacientes se reintervinieron posteriormente por evisceración y ninguno desarrolló nuevas fístulas. Dos pacientes presentaron nueva FE en otra localización y también fue tratada con SPN, resolviéndose. No se identificaron complicaciones derivadas del empleo de la presión negativa. Tras un seguimiento de 5 años, 3 niños recibieron posteriormente un trasplante multivisceral y 4 fallecieron [candidato a trasplante (1), encefalopatía (1), anemia hemolítica (1), sepsis de catéter (1)]. CONCLUSION: A pesar de nuestra serie limitada de pacientes proponemos este sistema como una herramienta útil en el manejo de FE y/o DPA.

Tuberculosis screening at a diabetes clinic in the Republic of the Marshall Islands.

SETTING: Tuberculosis (TB) and diabetes mellitus (DM) are prominent public health problems in the Republic of the Marshall Islands, a small island nation with high rates of tuberculosis and diabetes. OBJECTIVE: Evaluate the rate of active and latent TB in a Pacific Island DM clinic. DESIGN: In one DM clinic on the island of Ebeye, 213 adult patients aged 27-86 years completed tuberculin skin testing and TB work-up between April 2010 and March 2012. RESULTS: Screening for TB led to the diagnosis of 77 patients with TB infection and 11 patients with TB disease. From these data, the prevalence of TB disease among DM patients in the clinic exceeded 5% (95% CI 2.2%-8.1%). All patients who completed TB screening were at high risk of TB disease, and those with DM aged  ≤ 50 years had a higher risk of TB disease than those with DM over age 50 (RR 3.1, C.I. 1.0-9.7, p = 0.05). CONCLUSION: The experience at the Ebeye Diabetes Clinic demonstrates that screening DM patients for TB can identify significant rates of TB infection and TB disease, and should be considered for other settings with a high background TB incidence. Further assessment of TB risks should explore age, gender, and level of diabetes control.

Scaffold attachment factor B1 regulates the androgen receptor in concert with the growth inhibitory kinase MST1 and the methyltransferase EZH2.

The androgen receptor (AR) is a transcription factor that employs many diverse interactions with coregulatory proteins in normal physiology and in prostate cancer (PCa). The AR mediates cellular responses in association with chromatin complexes and kinase cascades. Here we report that the nuclear matrix protein, scaffold attachment factor B1 (SAFB1), regulates AR activity and AR levels in a manner that suggests its involvement in PCa. SAFB1 mRNA expression was lower in PCa in comparison with normal prostate tissue in a majority of publicly available RNA expression data sets. SAFB1 protein levels were also reduced with disease progression in a cohort of human PCa that included metastatic tumors. SAFB1 bound to AR and was phosphorylated by the MST1 (Hippo homolog) serine-threonine kinase, previously shown to be an AR repressor, and MST1 localization to AR-dependent promoters was inhibited by SAFB1 depletion. Knockdown of SAFB1 in androgen-dependent LNCaP PCa cells increased AR and prostate-specific antigen (PSA) levels, stimulated growth of cultured cells and subcutaneous xenografts and promoted a more aggressive phenotype, consistent with a repressive AR regulatory function. SAFB1 formed a complex with the histone methyltransferase EZH2 at AR-interacting chromatin sites in association with other polycomb repressive complex 2 (PRC2) proteins. We conclude that SAFB1 acts as a novel AR co-regulator at gene loci where signals from the MST1/Hippo and EZH2 pathways converge.

Seladin-1/DHCR24 protects neuroblastoma cells against Abeta toxicity by increasing membrane cholesterol content.

The role of brain cholesterol in Alzheimer's disease (AD) is currently a matter of debate. Experimental evidence suggests that reducing circulating and brain cholesterol protects against AD, however recent data indicate that low membrane cholesterol results in neurode-generation and that the cholesterol synthesis catalyst seladin-1 is down-regulated in AD-affected brain regions. We previously reported a significant correlation between resistance to amyloid toxicity and content of membrane cholesterol in differing cultured cell types. Here we provide evidence that Abeta42 pre-fibrillar aggregates accumulate more slowly and in reduced amount at the plasma membrane of human SH-SY5Y neuroblastoma cells overexpressing seladin-1 or treated with PEG-cholesterol than at the membrane of control cells. The accumulation was significantly increased in cholesterol-depleted cells following treatment with the specific seladin-1 inhibitor 5,22E-cholestadien-3-ol or with methyl-beta-cyclodextrin. The resistance to amyloid toxicity and the early cytosolic Ca2+ rise following exposure to Abeta42 aggregates were increased and prevented, respectively, by increasing membrane cholesterol whereas the opposite effects were found in cholesterol-depleted cells. These results suggest that seladin-1-dependent cholesterol synthesis reduces membrane-aggregate interaction and cell damage associated to amyloid-induced imbalance of cytosolic Ca2+. Our findings extend recently reported data indicating that seladin-1 overexpression directly enhances the resistance to Abeta toxicity featuring seladin-1/DHCR 24 as a possible new susceptibility gene for sporadic AD.

Sub-cellular localization of manganese in the basal ganglia of normal and manganese-treated rats An electron spectroscopy imaging and electron energy-loss spectroscopy study.

We have studied at the ultrastructural level the presence of manganese (Mn) in rat basal ganglia, which are target regions of the brain for Mn toxicity. The rats underwent a moderate level of Mn exposure induced per os for 13 weeks. Mn was detected by means of electron spectroscopy imaging (ESI) and electron energy-loss spectroscopy (EELS) analyses on perfusion fixed samples embedded in resin. While no significant contamination by exogenous Mn occurred during the processing procedures, less than 50% of endogenous Mn was lost during fixation and dehydration of the brain samples. The residual Mn ions in the samples appeared as discrete particles, localized in selected sub-cellular organelles in a cell, suggesting that no significant translocation had occurred in the surrounding area. In control rats, the Mn sub-cellular localization and relative content were the same in neurons and astrocytes of rat striatum and globus pallidus: the Mn level was highest in the heterochromatin and in the nucleolus, intermediate in the cytoplasm, and lowest in the mitochondria (p<0.001). After chronic Mn treatment, while no ultrastructural damage was detected in the neurons and glial cells, the largest rate of Mn increase was noted in the mitochondria of astrocytes (+700%), an intermediate rate in the mitochondria of neurons (+200%), and the lowest rate in the nuclei (+100%) of neurons and astrocytes; the Mn level in the cytoplasm appeared unchanged. EELS analysis detected the specific spectra of Mn L(2,3) (peak at DeltaE = 665 eV) in such organelles, confirming the findings of ESI. Although a consistent loss of Mn occurred during the processing of tissue samples, ESI and EELS can be useful methods for localization of endogenous Mn in embedded tissues. The high rate of Mn sequestration in the mitochondria of astrocytes in vivo may partly explain the outstanding capacity of astrocytes to accumulate Mn, and their early dysfunction in Mn neurotoxicity. The high level of Mn in the heterochromatin and nucleoli of neurons and astrocytes in basal conditions and its further increase after Mn overload should provide insight into new avenues of investigating the role of Mn in the normal brain and a baseline for future Mn toxicity studies.

Manganese intoxication decreases the expression of manganoproteins in the rat basal ganglia: an immunohistochemical study.

Manganese (Mn) is a cofactor for some metalloprotein enzymes, including Mn-superoxide dismutase (Mn-SOD), a mitochondrial enzyme predominantly localized in neurons, and glutamine synthetase (GS), which is selectively expressed in astroglial cells. The detoxifying effects of GS and Mn-SOD in the brain, involve catabolizing glutamate and scavenging superoxide anions, respectively. Mn intoxication is characterized by impaired function of the basal ganglia. However, it is unclear whether regional central nervous system expression of manganoproteins is also affected. Here, we use immunocytochemistry in the adult rat brain, to examine whether Mn overload selectively affects the expression of GS, Mn-SOD, Cu/Zn-SOD, another component of the SOD family, and glial fibrillary acid protein (GFAP), a specific marker of astrocytes. After chronic Mn overload in drinking water for 13 weeks, we found that the number and immunostaining intensity of GS- and Mn-SOD-positive cells was significantly decreased in the striatum and globus pallidus, but not in the cerebral frontal cortex. In addition, we found that GS enzymatic activity was decreased in the strio-pallidal regions but not in the cerebral cortex of Mn-treated animals. In contrast, Cu/Zn-SOD- and GFAP-immunoreactivity was unchanged in both the cerebral cortex and basal ganglia of Mn-treated rats. Thus, we conclude that in response to chronic Mn overload, a down-regulation of some manganoproteins occurs in neurons and astrocytes of the striatum and globus pallidus, probably reflecting the vulnerability of these regions to Mn toxicity.

Is dobutamine stress echocardiography predictive of middle and late term outcomes in mitral stenosis patients?

AIM: In mitral stenosis (MS) patients with a poor symptom-echocardiography correlation, dobutamine stress echocardiography (DSE) still does not have a confirmed utility and predictive value. Our aim is to evaluate usefulness of DSE in assessing 2 and 5 years clinical outcomes. METHODS: Forty-four consecutive patients with known MS were submitted, between April 1998 and July 1999, to basal and DSE. Patients were divided in 2 groups: group A if during DSE was reached a mean mitral gradient (MG) = or > 15 mmHg and/or a pulmonary arterial pressure (PAP) = or > 60 mmHg, and group B if MG and/or PAP were respectively lower than 15 and 60 mmHg. Endpoints considered were death, hospitalization for acute pulmonary edema, complications associated with mitral valve disease and mitral valve interventions (percutaneous or surgical). Mean follow-up was 73.6+/-16.6 months. RESULTS: Mean age was 55.2+/-10.5 years; 83.7% were women; NYHA class was I-II-III respectively in 18.6%, 58.1% and 23.3% of the patients; mean mitral valve area was 1.39+/-0.26 cm2; mean MG 8.05+/-2.54 mmHg; PAP 39.3+/-7.9 mmHg. Twenty-five patients met criteria for group A and 18 for group B. The event-free interval (27.9+/-32.1 months in group A vs 53.5+/-25.8 months in group B; P=0.008) and the 2 years event-free survival (40% for group A vs 88.9% for group B; P=0.002) showed significantly different patterns between the 2 groups. The 5 years survival analysis did not reach significance. CONCLUSION: DSE seems to detect MS patients that will have rapid evolution of their valvular disease within 24 months.

Effects of chronic internal alpha irradiation on physiology, growth and reproductive success of Daphnia magna.

Daphnids were chronically exposed to waterborne Am-241, an alpha-emitting radionuclide, ranging in concentration from 0.4 to 40 Bq ml(-1). Am-241 amounts were monitored in the medium, daphnid tissues and cuticles. Corresponding average dose rates of 0.02, 0.11 and 0.99 mGy h(-1) were calculated for whole organisms with internal alpha-radiation contributing 99% of total dose rates. Effects of internal alpha irradiation on respiration and ingestion rates, adult, egg and neonate individual dry masses, fecundity and larval resistance to starvation were examined in 23-day experiments. Daphnids showed increased respiratory demand after 23 days at the highest dose rate, suggesting increased metabolic cost of maintenance due to coping with alpha radiological stress. Although no effect was detected on ingestion rates between contaminated and control daphnids, exposure to dose rates of 0.11 mGy h(-1) or higher, resulted in a significant 15% reduction in body mass. Fecundity remained unchanged over the 23-day period, but individual masses of eggs and neonates were significantly smaller compared to the control. This suggested that increased metabolic expenditure in chronically alpha-radiated daphnids came at the expense of their energy investment per offspring. As a consequence, neonates showed significantly reduced resistance to starvation at every dose rate compared to the control. Our observations are discussed in comparison with literature results reported for cadmium, a chemical toxicant which affects feeding activity and strongly reduces individual energy uptake.

Severe degenerative aortic stenosis: when a senile patient is a candidate for surgery.

Senile aortic stenosis is characterized by calcific degeneration of the valve that prevents the full opening of the cusps in systole. The disease may be silent for many years despite the presence of severe flow obstruction and generally is associated with aortic regurgitation and calcification of the coronary arteries. The continuous increase of the aged population with aortic stenosis entails difficult decisions in selecting the candidates for aortic valve replacement in order to optimize the timing for surgery. Although clinical examination is still fundamental for the diagnosis of the disease and the screening of the population, noninvasive assessment by Doppler echocardiography has transformed the management of these patients. The procedure allows better identification of patients who may benefit from valve replacement in particular in the setting of a ''low output/low gradient'' state and permits a follow-up of the progression of the disease in patients who are not yet candidates for surgery. It also allows a decrease in the utilization of invasive hemodynamics becoming a cost benefit tool for the health system. When performed properly, it is relatively time consuming, needs experience but offers major anatomic and hemodynamic data. Under these circumstances, cardiac catheterization is required only in cases when there is discordance between the clinical assessment and cardiac ultrasound evaluation. In this review we summarize the prevalence and significance of the disease in the elderly population and the use of all recent echocardiographic data that may help select the true candidates for surgery.

Benign paroxysmal torticollis of infancy. A case report.

Benign paroxysmal torticollis of infancy is a benign, rare, probably under-recognised disorder, characterized by recurrent episodes of head tilting. The diagnosis is primarily one of pattern recognition and exclusion of alternatives conditions; other symptoms, such as vomiting, pallor and eyes' rotation, may be associated with or rapidly follow the attack, leading to misdiagnosis of this disease. The exact pathogenesis of benign paroxysmal torticollis is not clear, but a close relationship with childhood periodic syndromes is supposed. Due to the difficulty in defining the disease, this event has implications with respect to the training and education of practice providers and emergency physicians. We describe the case of a 7-month-old infant with benign paroxysmal torticollis recently observed, discuss the clinical presentation and review the literature.

The Myocardial Performance Index detects chronic cardiac allograft dysfunction sooner than other methods.

AIM: Many noninvasive techniques have been proposed for the early detection of chronic heart graft dysfunction. Diastolic dysfunction may precede systolic dysfunction, and often is prominent; therefore, the aim of the study was to investigate the clinical and prognostic value of a Doppler-derived index of both systolic and diastolic function in heart transplanted patients (Myocardial Performance Index, MPI). METHODS: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls. A complete clinical examination was performed at the time of enrollment and was repeated after 3 months. RESULTS: At 3 months, 11 patients (17.5%) presented events (heart failure, hospitalisation or cardiac death). Patients were divided into 2 groups: Group A (52 patients) without events in the follow-up and Group B (11 patients) with events. The values of MPI in Group B (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18, P=0.001). Whereas the values of the index did not differ significantly between Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate analysis, the population of heart transplanted patients was dichotomised in subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%. Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%) with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50% had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2 14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF (chi squared=20.8, P=0.025) were significant independent predictors of heart failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be better than EF in the earlier detection of graft dysfunction. CONCLUSION: MPI, as a combined systolic and diastolic index, may detect graft dysfunction earlier than EF.

Influence of rainfall characteristics on elimination of aerosols of cesium, strontium, barium and tellurium deposited on grassland.

This work is aimed at quantifying foliar transfer of cesium, strontium, barium and tellurium under the influence of rainfall characteristics (intensity, frequency and time elapsed between contamination and first rainfall). Grassland boxes were contaminated by dry deposition of multi-element aerosols of (137)Cs, (85)Sr, (133)Ba and (123m)Te. They were grown in a greenhouse under controlled conditions. The treatments consisted of mowing and applying rainfalls (8 and 30 mmh(-1)) at different times after the contamination. At a leaf area index of 5.9+/-1.9, interception of the aerosols was similar for the 4 radionuclides (83.8+/-5.9%). Dew produced significant radionuclide accumulation in the base of the vegetation and transfer to the soil. For moderate intensity, an early (2 days after contamination) first rainfall was as efficient, in terms of leaf wash-off, as a longer rainfall occurring later (6 days after contamination). For early rainfalls, eliminated activities were comparable because the influence of rain intensity was compensated by rain duration. However, for late rainfalls, wash-off efficiency increased with rainfall intensity. Total transfer factors (TTF) were determined on whole grass immediately after 4 rainfalls and at harvest. After 4 medium intensity rainfalls, rain frequency did not influence total transfer factors (TTF) of strontium, barium and tellurium (about 0.2, 0.3 and 0.35 Bq kg(fresh weight)(-1) by Bq m(-2), respectively). Cesium TTF value was lower in the case of a weekly rain (0.1 against 0.2 Bq kg(fresh weight)(-1) by Bqm(-2)). TTF values were similar for twice-a-week rainfalls, whatever their intensity. They were higher for weekly rains of high intensity (between 0.3 and 0.75 Bq kg(fresh weight)(-1) by Bqm(-2) against 0.1-0.35 Bq kg(fresh weight)(-1) by Bq m(-2), depending on the radionuclides). TTF values attested that wash-off was more efficient when rainfalls lasted longer. Field loss on the top of the leaves was well described by an offset exponential model. The half-lives varied with rainfall characteristics from 4 days for cesium, strontium and barium to 20 days for tellurium. The offset value varied between 0% for tellurium (high intensity rainfalls) and 14% for cesium (medium intensity rainfalls).