Considerations about the Geographic Distribution of Histoplasma Species.

Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. Histoplasma has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, Histoplasma taxonomy is adjusting to new genetic data. Here, we have suggested that Histoplasma has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. Histoplasma's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.

Correlation Between Amyloid PET Imaging and Discordant Cerebrospinal Fluid Biomarkers Results in Patients with Suspected Alzheimer's Disease.

BACKGROUND: Although the concordance between cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and amyloid-PET findings is well known, there are no data regarding the concordance of amyloid-PET with inconclusive CSF values of amyloid-ß (Aß)1 - 42 and p-tau for the diagnosis of AD. OBJECTIVE: To investigate the relationship between the amyloid-PET results with discordant AD biomarkers values in CSF (Aß1 - 42+/p-tau-or Aß1 - 42-/p-tau+). METHODS: An observational retrospective study, including 62 patients with mild cognitive impairment (32/62) or dementia (30/62), suspicious of AD who had undergone a lumbar puncture to determine CSF AD biomarkers, and presented discordant values in CSF between Aß1 - 42 and p-tau (Aß1 - 42+/p-tau-or Aß1 - 42-/p-tau+). All of them, underwent an amyloid-PET with 18F-Florbetaben. An extensive neuropsychological testing as part of their diagnostic process (MMSE and TMA-93), was performed, and it was also obtained the Global Deterioration Scale. RESULTS: Comparing the discordant CSF results of each patient with the cerebral amyloid-PET results, we found that in the group with Aß1 - 42+ and p-tau-CSF values, the amyloid-PET was positive in 51.2% and negative in 48.8% of patients, while in the group with Aß1 - 42-and p-Tau+ CSF values, the amyloid-PET was positive in 52.6% of patients and negative in 47.4% of them. No significant association was found (p = 0.951) between the results of amyloid-PET and the two divergent groups in CSF. CONCLUSIONS: No significant relationship was observed between the results of discordant AD biomarkers in CSF and the result of amyloid-PET. No trend in amyloid-PET results was observed in relation to CSF biomarker values.

Molecular detection of Histoplasma capsulatum in the lung of a free-ranging common noctule (Nyctalus noctula) from France using the Hcp100 gene.

Histoplasma capsulatum is a dimorphic fungus that is widely distributed in the tropical or subtropical areas of the world and infects several mammalian hosts, mainly bats. Infective propagules grow in bat and bird droppings. A specific molecular marker, a highly sensitive fragment of a co-activator protein-coding gene (Hcp100), was used to detect H. capsulatum in lung samples of wild and captive bats from France using a nested polymerase chain reaction. To determine whether bats in France are potential carriers of H. capsulatum, 83 bats were sampled from two regions in France. Sixty-one specimens belonging to the Pteropus rodricensis (n = 45) and Rousettus aegyptiacus (n = 16) species were collected from a zoologic park (La Palmyre, western France). Twenty-two specimens were recovered from the Natural History Museum (Bourges) including the species Plecotus austriacus (n = 1), Pipistrellus pipistrellus (n = 3), and Nyctalus noctula (n = 18). From the lung DNA samples of 83 dead bats, only one sample of an N. noctula bat from Bourges amplified the H. capsulatum Hcp100 marker. The amplified product was sequenced and revealed a high similarity to the G217B H. capsulatum reference strain sequence that was deposited in the GenBank database. This finding suggests that H. capsulatum is an environmental pathogen in France that may infect bats.

[Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases]. / Técnica del ganglio centinela en el cáncer de colon. Experiencia en 125 casos.

INTRODUCTION: The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. MATERIALS AND METHODS: A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. RESULTS: The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006). CONCLUSIONS: Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii, indicating chemotherapy that may improve their prognosis.

Central Nervous System Histoplasmosis: An Updated Insight.

Histoplasmosis is one of the systemic mycoses that can involve the Central Nervous System (CNS), and it is caused by the dimorphic ascomycete species of the Histoplasma capsulatum complex. Once in the CNS, this pathogen causes life-threatening injuries that are associated with clinical manifestations of meningitis, focal lesions (abscesses, histoplasmomas), and spinal cord injuries. The present review provides updated data and highlights a particular vision regarding this mycosis and its causative agent, as well as its epidemiology, clinical forms, pathogenesis, diagnosis, and therapy, focusing on the CNS.

The effects of 17ß-oestradiol on increased α(1)-adrenergic vascular reactivity induced by prolonged ovarian hormone deprivation: the role of voltage-dependent L-type Ca channels.

The present study investigated the hypothesis that the duration of ovarian hormone deprivation before reintroduction of oestrogen affects the role of oestrogen as a mediator of the contractile function of α(1)-adrenergic receptors. Rats underwent ovariectomy (OVX) or were sham-operated, and the OVX rats were treated with vehicle (corn oil) or 17ß-oestradiol (E(2)) for 5 days either 10, 28 or 60 days after OVX. The OVX increased phenylephrine- and Ca(2+)-induced contractions. Interestingly, the phenylephrine-induced contractions were increased at each of the three time points, whereas the Ca(2+)-induced contractions were only increased in the 60-day group. E(2) had biphasic effects on phenylephrine- and Ca(2+)-induced contractility. Indeed, E(2) increased contractions in the 10-day group and diminished contractions in the other groups (the increased contractions were avoided by verapamil). These results indicate that E(2) controls α(1)-adrenergic receptor-mediated contractility through effects on L-type Ca(2+) channels in a way that depends on the timing in which the treatment with E(2) is initiated.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Differential diagnosis of HaNDL syndrome in a case report of a pediatric patient: The role of SPECT with 99mTc-HMPAO.

•HaNDL syndrome may be a condition probably underdiagnosed in pediatric age.•A differential diagnosis with viral, vascular or autoimmune etiology is necessary.•Epileptiform alterations in EEG could be possible in this infrequent syndrome.•99mTc-HMPAO SPECT provides a potential role in the differential diagnostic and management.

Histoplasma capsulatum and Pneumocystis jirovecii coinfection in hospitalized HIV and non-HIV patients from a tertiary care hospital in Mexico.

BACKGROUND: Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely reported. This study detected this coinfection using specific molecular methods for each fungus in the bronchoalveolar lavage (BAL) of patients from a tertiary care hospital. MATERIALS AND METHODS: BAL samples from 289 hospitalized patients were screened by PCR with specific markers for H. capsulatum (Hcp100) and P. jirovecii (mtLSUrRNA and mtSSUrRNA). The presence of these pathogens was confirmed by the generated sequences for each marker. The clinical and laboratory data for the patients were analyzed using statistical software. RESULTS: The PCR findings separated three groups of patients, where the first was represented by 60 (20.8%) histoplasmosis patients, the second by 45 (15.6%) patients with pneumocystosis, and the last group by 12 (4.2%) patients with coinfection. High similarity among the generated sequences of each species was demonstrated by BLASTn and neighbor-joining algorithms. The estimated prevalence of H. capsulatum and P. jirovecii coinfection was higher in HIV patients.

Mixed infection by Histoplasma capsulatum isolates with different mating types in Brazilian AIDS-patients.

Mixed infection by Histoplasma capsulatum isolates with different mating types, in AIDS-patients are described in this study. Morphological, mating type-specific PCR assay and multilocus sequencing type analysis of H. capsulatum isolates recovered from two Brazilian AIDS-patients were performed. Five H. capsulatum isolates were recovered at different times from the two patients. Three isolates were obtained from bone marrow (day 1 - CE0411) and buffy coat cultures (day 1 - CE0311; day 2 - CE0511) of patient 1, and two isolates were isolated from buffy coat cultures (day 3 - CE2813; day 12 - CE2513) of patient 2. The mycelial colonies depicted different textures and pigmentation features. Dimorphic conversion to the yeast-phase in ML-Gema medium was achieved in all isolates. MAT1-1 idiomorph was identified in CE0311, CE0411 and CE2813 isolates; MAT1-2 idiomorph was found in CE0511 and CE2513 isolates. These H. capsulatum isolates were grouped within LAm A clade, highlighting that CE0311 and CE0411 isolates formed a subgroup supported by a high bootstrap value. The CE0511, CE2513, and CE2813 isolates clustered together with a Brazilian H151 isolate. This research reports mixed infections caused by H. capsulatum isolates with different mating types in Brazilian AIDS-patients for the first time in the literature.

Novel clinical and dual infection by Histoplasma capsulatum genotypes in HIV patients from Northeastern, Brazil.

Histoplasmosis is a worldwide-distributed deep mycosis that affects healthy and immunocompromised hosts. Severe and disseminated disease is especially common in HIV-infected patients. At least 11 phylogenetic species are recognized and the majority of diversity is found in Latin America. The northeastern region of Brazil has one of the highest HIV/AIDS prevalence in Latin America and Ceará State has one of the highest death rates due to histoplasmosis in the world, where the mortality rate varies between 33-42%. The phylogenetic distribution and population genetic structure of 51 clinical isolates from Northeast Brazil was studied. For that morphological characteristics, exoantigens profile, and fungal mating types were evaluated. The genotypes were deduced by a MSLT in order to define local population structure of this fungal pathogen. In addition, the relationships of H. capsulatum genotypes with clinically relevant phenotypes and clinical aspects were investigated. The results suggest two cryptic species, herein named population Northeast BR1 and population Northeast BR2. These populations are recombining, exhibit a high level of haplotype diversity, and contain different ratios of mating types MAT1-1 and MAT1-2. However, differences in phenotypes or clinical aspects were not observed within these new cryptic species. A HIV patient can be co-infected by two or more genotypes from Northeast BR1 and/or Northeast BR2, which may have significant impact on disease progression due to the impaired immune response. We hypothesize that co-infections could be the result of multiple exposure events and may indicate higher risk of disseminated histoplasmosis, especially in HIV infected patients.

Causas de muerte de los fallecidos en hemodiálisis iterada

Introducción: La hemodiálisis es la terapia de remplazo renal más utilizada en Latinoamérica y en Cuba. Se calcula que para el año 2030 la cantidad de pacientes que inician el tratamiento de reemplazo renal a nivel mundial aumentará a más del 50 % con respecto al año 2010. Objetivo: Caracterizar los pacientes en tratamiento de hemodiálisis iterada. Métodos: Se realizó un estudio descriptivo, transversal, de todos los pacientes en tratamiento de HDI del Instituto de Nefrología "Dr. Abelardo Buch López" (INEF), fallecidos en el período 2013-2018. Los datos se obtuvieron del registro de fallecidos, del registro de pacientes en hemodiálisis y de la historia clínica. El procesamiento fue realizado de forma automatizada (IBM Spss 22.0). Se calcularon tasas brutas de mortalidad y fue utilizada la técnica de análisis de distribución de frecuencias. Resultados: La tasa de mortalidad del período resultó ser 20,3 por cada 100 pacientes. El 60,9 % de los pacientes fallecidos tenían entre 60 y 79 años de edad. La hipertensión arterial (HTA) fue la enfermedad de base más frecuente (55,5 %), y la comorbilidad predominante (87,3 %). El 53,6 % de los pacientes fallecidos empleaba catéter venoso central, y el 70 % tenía menos de 5 años en HD. La principal causa de muerte fue la enfermedad cardiovascular (46,4 %). Conclusiones: En el INEF la mortalidad en hemodiálisis se comportó de manera estable. Similar a otros reportes de servicios de hemodiálisis, los fallecidos se caracterizaron en su mayoría por tener catéter venoso central para hemodiálisis y menos de cinco años en el tratamiento. Las causas de muerte presentaron el mismo patrón que las reportadas en análisis nacionales e internacionales.

Introduction: Hemodialysis is the most used renal replacement therapy in Latin America and in Cuba. It is estimated that by the year 2030 the number of patients starting therapy worldwide will increase to more than 50% compared to 2010. Objectives: To characterize the patients undergoing iterated hemodialysis treatment. Methods: A descriptive, cross-sectional study of all patients undergoing repeated hemodialysis treatment, who deceased in the period 2013-2018 was carried out at Dr. Abelardo Buch López Institute of Nephrology. The processing was done in an automatically (IBM Spss 22.0). Gross mortality rates were calculated and the frequency distribution analysis technique was used. Results: The mortality rate for the period was 20.3 per 100 patients. 60.9% of the deceased patients were between 60 and 79 years of age. Arterial hypertension was the most frequent underlying disease (55.5%), and the predominant comorbidity (87.3%). 53.6% of the deceased patients used a central venous catheter, and 70% had been on hemodialysis for less than 5 years. The main cause of death was cardiovascular disease (46.4%). Conclusions: At Dr. Abelardo Buch López Institute of Nephrology mortality in hemodialysis behaved in a stable manner. Similar to other reports of hemodialysis services, the deceased were mostly characterized by having a central venous catheter for hemodialysis and less than five years in treatment. The causes of death showed the same pattern as those reported in national and international analyses.

Factores relacionados con la supervivencia de pacientes que inician tratamiento de hemodiálisis. Instituto de Nefrología / Factors related to the survival of patients who start receiving hemodialysis. Institute of Nephrology

Introducción: La enfermedad renal crónica constituye un problema de salud por su impacto sobre los individuos, la sociedad y la economía. Existe un insuficiente conocimiento de los factores relacionados con la supervivencia en los pacientes que inician hemodiálisis en nuestro medio. Objetivo: Identificar los factores relacionados con la supervivencia de los pacientes que iniciaron hemodiálisis. Material y Métodos: Se realizó un estudio descriptivo de corte retrospectivo, de pacientes que iniciaron hemodiálisis en el Instituto de Nefrología Dr. Abelardo Buch en el período del 1 de enero de 2011 al 31 de diciembre de 2016. Se analizaron variables sociodemográficas y clínicas, y se realizó una correlación de estas con la supervivencia en hemodiálisis. Para todas las pruebas realizadas se fijó un nivel de significación ɑ= 0.05. Resultados: Se estudiaron 81 pacientes, con edad media de 55 años y predominio del sexo masculino (61,7 por ciento) y la raza blanca (59,3 por ciento). Los resultados estadísticamente significativos fueron la desnutrición (Índice de Masa Corporal < 18.5 kg/m2), con una mediana de supervivencia de (7,6+-4,9; log Rank: 0,015), las cifras de albúmina sérica menores a 35 g/L, con (33.1 +-5.4; log Rank: 0.050) la falta de seguimiento nefrológico previo, con (21,5 +-2,6; log Rank: 0,041), y el empleo de catéter venoso central como acceso vascular, con (32,4+-3,5; log Rank: 0,038). Conclusiones: La desnutrición, la hipoalbuminemia, el empleo de catéter venoso central como acceso vascular y la falta de seguimiento nefrológico previo afectaron negativamente la supervivencia de los pacientes en hemodiálisis(AU)

Introduction: Chronic kidney disease is a health problem because of its impact on individuals, society and the economy. There is not enough knowledge of the factors related to survival in patients who start hemodialysis in our environment. Objective: To identify the factors related to the survival of patients who started receiving hemodialysis. Material and Methods: A descriptive retrospective study was conducted in 81 patients who started receiving hemodialysis in the Dr. Abelardo Buch Institute of Nephrology in the period between January 1, 2011 and December 31, 2016. Sociodemographic and clinical variables were analyzed. A correlation between these variables and survival was made. The level of significance in all the tests performed was determined to be ɑ= 0.05. Results: A total of 81 patients were studied. The mean age was 55 years. The male sex (61,7 percent) and the white race (59,3 percent) predominated in the study. The statistically significant variables were malnutrition (body mass index < 18.5 kg/m2) with a median survival of (7,6+-4,9; log rank: 0,015), serum albumin levels lower than 35 g/L, with (33.1 +-5.4; log rank: 0.050), lack of previous nephrological follow-up, with (21,5 +-2,6; log rank: 0,041) and the use of central venous catheter as vascular access with (32,4+-3,5; log rank: 0,038). Conclusions: Malnutrition, hypoalbuminemia, the use of central venous catheter as vascular access and previous nephrological follow-up negatively affected the survival of patients on hemodialysis (AU)

Susceptibilidad antimicrobiana de bacterias aisladas en sepsis del acceso vascular. Instituto de Nefrología, 2019 / Antimicrobial susceptibility of bacteria isolated from vascular access sepsis. Institute of Nephrology, 2019

Introducción: El acceso vascular en hemodiálisis es esencial para el enfermo renal por su repercusión en la calidad de vida. La fístula arteriovenosa, los catéteres para hemodiálisis o las prótesis vasculares, aunque han evolucionado gradualmente hacia el perfeccionamiento, son proclives a las infecciones debidas fundamentalmente a bacterias de la microbiota de la piel y mucosas. Objetivo: Caracterizar la susceptibilidad antimicrobiana de las bacterias aisladas de pacientes con sepsis del acceso vascular en el servicio de hemodiálisis del Instituto de Nefrología. Material y Métodos: Estudio de corte transversal, en el período comprendido entre enero a diciembre de 2019. El universo estuvo constituido por 112 aislamientos obtenidos a partir de muestras de hemocultivos, secreciones y puntas de catéter de los pacientes con bacteriemias, sepsis o secreción en el sitio de inserción del catéter o acceso vascular. Resultados: El 72,3 por ciento de las muestras estudiadas fueron hemocultivos. Se obtuvo 38,3 % de aislamientos de Staphylococcus aureus, sensibles en su totalidad a la vancomicina. El 68,1 % de las cepas de Escherichia coli fueron productoras de betalactamasas de espectro extendido (BLEE) con sensibilidad superior a 60 % a aminoglucósidos y carbapenémicos; similar patrón de sensibilidad mostraron las cepas de Pseudomonas, no obstante, el 100% fue resistente a las cefalosporinas. Conclusiones: No se reportó resistencia a la vancomicina en el estudio. Los aislamientos de los gérmenes gramnegativos mostraron elevada resistencia a las cefalosporinas y una buena sensibilidad a aminoglucósidos y carbapenémicos(AU)

Introduction: The vascular access in hemodialysis is essential for the renal patient both for its associated morbidity and mortality as well as for its impact on quality of life. Although arteriovenous fistula, hemodialysis catheters or vascular prostheses have gradually evolved toward improvement, they are prone to infections primarily due to bacteria on the skin and mucosal microbiota. Objective: To characterize the antimicrobial susceptibility of bacteria isolated from patients with vascular access sepsis in the hemodialysis service of the Institute of Nephrology. Material and Methods: A cross-sectional study was conducted in the period January-December 2019. The universe consisted of all 112 isolates obtained from blood culture samples, secretions and catheter tips from patients with bacteremia, sepsis or discharge at the site of catheter insertion or vascular access. Results: The results show that 72.3% of the samples studied were blood cultures. Also, 38.3 percent of Staphylococcus aureus isolates, which were totally sensitive to vancomycin, were obtained. On the other hand, 68.1% of Escherichia coli strains were extended spectrum beta-lactamases (ESBL) producers with sensitivity to aminoglycosides and carbapenems greater than 60%. Pseudomonas strains exhibited a similar pattern of sensitivity, however, 100% were resistant to cephalosporins. Conclusions: No resistance to vancomycin was reported in this study. Gram-negative isolates showed high resistance to cephalosporins and good sensitivity to aminoglycosides and carbapenems(AU)

Retinal nerve fiber layer thinning in Parkinson disease.

Retinal dopamine loss in Parkinson disease (PD) is reflected by visual neurophysiological dysfunction. We measured the thickness of the circumpapillary retinal nerve fiber layer (RNFL) in PD patients using optical coherence tomography. The thickness in the inferior quadrant of PD patients (147 +/- 20 microns) was significantly thinner than that of controls (173 +/- 12 microns; p=0.002), while the inferotemporal area was the thinnest (146 +/- 24 vs. 191 +/- 21 microns; p=0.0003). The results show significant loss of RNFL thickness in PD at specific sites.

Palladium(II) Complexation by p-Cyclophane Receptors. A Solution and Solid State Study.

The coordination properties of the macrocyclic ligands 1,4,7,16,19,22-hexamethyl-1,4,7,16,19,22-hexaaza[9.9]-p-cyclophane (L1) and 1,4,7-trimethyl-19,22,28,31-tetraoxa-1,4,7,14,23-pentaaza[9.25]-p-cyclophane (L2) have been studied by means of potentiometric and (1)H and (13)C measurements in aqueous solution. L1 is composed of two equal triamine binding units connected by p-phenylene spacers. L2 presents a similar molecular architecture, a triamine moiety of L1 being replaced by a cyclic N(2)O(4) binding unit. L1 can form both mono- and dinuclear complexes in aqueous solution, while L2 gives only mononuclear species. The potentiometric data indicate that in the L1 dinuclear complex each metal is coordinated by a triamine moiety. In the L2 mononuclear complex the Pd(II) ion is coordinated by the N(3) unit. The N(2)O(4) moiety does not show any binding ability toward Pd(II), but exhibits a high tendency to protonate. These solution data are confirmed by the crystal structures of [Pd(2)Cl(2)L1](ClO(4))(2).H(2)O (a) and [PdClL2H(2)(H(2)O)](ClO(4))(3) (b). In complex a, each Pd(II) ion is four coordinated by the three amine groups of the triaza moiety and a chloride anion, in a square planar geometry. In the mononuclear complex b, the metal is coordinated by the N(3) moiety, with a coordination environment almost equal to that found in complex a. The N(2)O(4) moiety is diprotonated and encapsulates in its cavity a water molecule, held by a hydrogen-bond network. The solution structures of the L1 and L2 complexes have been studied by means of (1)H and (13)C NMR measurements. The analysis of the NMR data reveals that the dinuclear L1 complex and the L2 mononuclear one show structural features in solution almost equal to those found in the solid state. Solution and solid state data indicate that the Pd(II) complexation gives a marked stiffening of the macrocyclic structures.

Effect of Nitrogen Methylation on Cation and Anion Coordination by Hexa- and Heptaazamacrocycles. Catalytic Properties of These Ligands in ATP Dephosphorylation.

The stability constants of the complexes formed by 1,10-dimethyl-1,4,7,10,13,16-hexaazacyclooctadecane (L) and 1,4,7-trimethyl-1,4,7,10,13,16,19-heptaazacyclohenicosane (L1) with Ni(2+), Cu(2+), Zn(2+), Cd(2+), and Pb(2+), as well as that for the formation of PbL2(2+) (L2 = 1,4,7,13-tetramethyl-1,4,7,10,13,16-hexaazacyclooctadecane), were determined by means of potentiometric (pH-metric) titrations in 0.15 mol dm(-)(3) NaClO(4) at 298.1 +/- 0.1 K. The enthalpy changes for the formation of Cu(2+) complexes with L and L1 were measured by means of microcalorimetry. These thermodynamic data were compared with those previously reported for L2, 1,4,7,10,13,16-hexaazacyclooctadecane (L3), and 1,4,7,10,13,16,19-heptaazacyclohenicosane (L4) evidencing that nitrogen methylation can produce lower or higher complex stability depending on the metal ion and the number of methylated nitrogens. The equilibria of complexation of ATP(4)(-), ADP(3)(-), AMP(2)(-), P(2)O(7)(4)(-), and [Co(CN)(6)](3)(-) by Land L1 were studied by means of pH-metric titrations in 0.15 mol dm(-)(3) NaClO(4) at 298.1 +/- 0.1 K. The catalytic reactions of ATP dephosphorylation induced by these ligands in solution were followed by (31)P NMR spectroscopy at different temperature and pH values. L is the most appropriate receptor, among L-L4, in the recognition of the nucleotide. The catalytic efficiency of hexa- and heptaazaligands increases in the order L < L3 < L2 and L1 < L4, respectively, L4 being the most efficient. Namely, di- and tetramethylation of L3 produces opposite effects on its catalytic properties.

Effect of amiodarone on haemodynamics during cardiopulmonary resuscitation in a canine model of resistant ventricular fibrillation.

OBJECTIVE: Amiodarone has been shown to be superior to both placebo and lidocaine in improving survival to hospital admission for victims of out-of-hospital refractory ventricular fibrillation. Concern had been expressed about the known vasodilatatory effects of amiodarone if given without precedent vasoconstrictive medications. The haemodynamic effects of intravenous amiodarone administered during ongoing CPR have not been systemically investigated. Our intention was to verify if amiodarone alone produced significantly lower resuscitation haemodynamics than did either adrenaline (epinephrine) alone or the combination of amiodarone and adrenaline. DESIGN: Prospective, randomized, comparative study. SETTING: Research laboratory of a medical school. SUBJECTS: Thirty mongrel dogs. INTERVENTIONS: After 8 min of untreated VF, defibrillation was attempted once at 3 J/kg and external chest compressions and ventilation started. Those animals resistant to the defibrillation attempt were randomized, ten to an adrenaline (0.02 mg/kg) group, ten to an amiodarone (5 mg/kg) group, and ten to a group receiving a combination of both drugs. MEASUREMENTS AND MAIN RESULTS: Aortic systolic and diastolic, and coronary perfusion pressures were all significantly lower in the group receiving amiodarone alone than in the other two groups. Amiodarone combined with adrenaline produced pressures during CPR similar to adrenaline alone. CONCLUSION: Amiodarone can be safely administered simultaneously in combination with adrenaline and such a combination results in similar haemodynamic support as adrenaline alone. Amiodarone administered alone produces significantly lower coronary perfusion pressure than when combined with adrenaline.

Hydrogenation of White Phosphorus to Phosphane with Rhodium and Iridium Trihydrides.

Only one of the four P atoms of P4 reacts with rhodium and iridium trihydrides [(triphos)MH3 ] to provide phosphane [Eq. (a)]. The resulting cyclo-P3 fragment is efficiently scavenged by the metal fragment to give the complexes [(triphos)M(η3 -P3 )]. A mechanism accounting for the hydrogenation reaction is proposed in which the complexes [(triphos)MH(η1 :η1 -P4 )] and [(triphos)M(η1 :η2 -HP4 ] are intermediates. The latter complex contains the unprecedented hydridotetraphosphane ligand HP4- .