Retracing the evolutionary history of Nothofagus in its geo-climatic context: new developments in the emerging field of phylogeology.

Phylogeographic studies have made a significant contribution to the interpretation of genetic lineage distribution in response to climate changes, such as during glaciation events of the Neogene. However, the effects of ancient landscapes associated with global sea level rises, tectonic processes, and climatology driving lineage evolution have been largely overlooked. These effects can be tested in widespread lineages of cold-tolerant species that have endured cooling, and thus, phylogeographic patterns may reflect large-scale processes that were not reset by the ice ages. We hereby combine geological evidence from marine sedimentary basins, Andean orogeny, and climatology with molecular dating and statistical phylogeography to infer how geological and climatic processes affected the distribution of lineages in cold-tolerant Nothofagus species during the Cenozoic. A total of 239 populations along the entire range of all species within the genus Nothofagus (N. antarctica, N. betuloides, N. dombeyi, N. nitida, and N. pumilio) were sampled and analyzed by sequencing three non-coding regions of the chloroplast. We found 30 chloroplast DNA haplotypes that were geographically structured. Molecular dating calibrated with fossils revealed that ancestral lineages appeared in Eocene/Oligocene, whereas most divergences took place during the Miocene; in turn, Bayesian skyline plots showed that population expansion occurred in the Early Pleistocene (1.5-1 million years ago). Lineage divergence from all wide-ranging Nothofagus was spatially and temporally concordant with episodic marine transgressions and warmer times in Patagonia during Eocene/Miocene Epochs. Long-lasting stable raised areas preserved haplotype diversity throughout Patagonia, from where cold-tolerant taxa expanded their ranges during pre-Quaternary times. The detailed study of such ancient divergences is novel and allows us to infer the effects of geological processes on distribution patterns of ancient lineages, that is, phylogeology.

Issues of internal medicine in psychiatric patients.

In opposition to opinions of a sectorialization of psychiatric illness, phenomena of comorbidity due to susceptibility of psychiatric patients to contract other diseases--whose co-presence is difficult to translate and treat--are more and more evident. In this review we have marked main issues of internal medicine in psychiatric patients. This review will discuss particularly main cardiovascular diseases (CAD, VTE), lung diseases (COPD,asthma, restrictive lung disease) gastroenterologic disease (IBS, coeliac disease, ulcerous rectocolitis), diabetes and metabolic syndrome, more likely infections verified in these patients (HIV, viral hepatitis), cancers considerably underlined (breast cancer, colon-rectal cancer and lung cancer), internistic issues in alcohol abuse which is a frequent state in these subjects. A special chapter is dedicated to antipsychotics. These drugs are characterized by a complex action modality and by frequent interactions with a large number of other drugs.

Male sexual disturbances in liver diseases: what do we know?

The alterations of sexual function known as the erectile dysfunction are quite frequent among patients affected by liver diseases and they tend to increase in advanced liver failure. This process is directly linked to cirrhosis or its treatments, such as liver transplantation, or to certain drugs (e.g. beta-blockers). Independent of cirrhosis, other factors may cause sexual problems in these patients. Alcohol itself seems to worsen sexual function in the absence of cirrhosis. Viral hepatitis has an uncertain influence on male gonadic function and even antiviral therapy itself can worsen some seminal and hormonal parameters, although it is reversible. Quality of life may be greatly decreased in cases of cirrhosis where these alterations are present, so it is important to value and care for them, if possible. This review investigates the major male sexual disturbances in liver diseases of various origins.

Characteristics of liver diseases in the elderly: a review.

Chronic liver diseases are becoming more commonly diagnosed in the elderly, although they are not age-related. Most liver functions in advanced age appear to be well preserved, but some changes in liver morphology and physiology with aging may lead to several differences in clinical course and management of liver diseases in older patients compared to younger. A cautious individual evaluation is therefore required in aged patients, especially concerning reduced hepatic drug clearance and comorbidity. Many chronic liver diseases are characterized by a slow and indolent course with non-specific clinical presentation and this may lead a later diagnosis in the elderly. The presence of an advanced liver disease or cirrhosis is more frequent in old patients as the first clinical presentation. No significant differences in diagnostic investigations or treatment options occur between the elderly and the young. Hepatocellular carcinoma is an affliction of the old patients (mean age 65 age) and follow up with ultrasonography and alpha-fetoprotein is mandatory. Advanced age is not considered a contraindication to liver transplantation, but recipients older than 60 years with poor hepatic synthetic function and comorbidity show a worse prognosis with lower survival rates. This review focuses on new emerging conditions, clinical features and updated therapeutic approaches of the most common chronic liver diseases among the elderly.

Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis.

INTRODUCTION: Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease. AIM: To investigate factors potentially preventing atherosclerosis in PBC patients. METHODS: Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 +/- 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome. RESULTS: The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 +/- 50.5 mg/dL in PBC vs 221.7 +/- 39.7 mg/dL in NASH vs 209.8 +/- 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase. CONCLUSIONS: The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

Gastrointestinal problems in the elderly.

Gastrointestinal (GI) disorders represent the third cause of consultations by general practitioners among subjects older than 65 years in Western countries. Although GI diseases in the elderly do not show peculiar characteristics, they often may present a more severe course, due to comorbidities and intake of many drugs. Moreover, several illnesses, such as neoplasias, are more frequent in the elderly. This review focuses on the epidemiological, physiopathological, and clinical aspects of GI diseases in advanced age. Some relevant issues are considered. It is advisable to avoid empirical approaches in the elderly and to choose endoscopic examinations because of the possibility to detect conditions such as already complicated gastroesophageal reflux disease or peptic ulcers as well as to diagnose precociously neoplastic formations in esophagus, stomach or colon. The monitoring of chronic liver disease is very important, mainly to prevent or detect hepatocellular carcinoma early. Idiopathic (or autoimmune) chronic pancreatitis in the elderly is more frequent than other forms of pancreatic diseases, like alcoholic pancreatitis.

Diagnostic and therapeutic questions in overlap syndromes of autoimmune hepatitis.

The term ''overlap syndromes of liver diseases'' includes coexistence of autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC). Due to their unknown etiology, as well as their variable presentation with mixed clinical and biochemical features, these overlap syndromes are often a diagnostic and therapeutic challenge for hepatologists. The most frequent association reported occurs between AIH and PBC. More rare is the overlap between AIH and PSC, typical in young age and often concomitant with an inflammatory bowel disease as ulcerative colitis. The treatment of choice is based on ursodeoxycholic acid and immunosoppressive drugs, used at the same time or consecutively, according to the course of disease. Histological examination seems an important tool, but often does not help for a correct diagnosis due to lack of specificity. Two particular forms of variant syndrome are the so called outlier syndromes, without clear characteristics of overlap: the autoimmune cholangitis, probably a form of PBC anti-mitochondrial antibodies negative, and the hepatitis C virus related with stigmata of autoimmunity, such as nonspecific autoantibodies at low titer. The diagnostic score system elaborated in 1999 by the International AIH Group can help for diagnosis, even if its definite validity is lacking.

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study.

BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre-Hepatitis C era' and data on the natural history are still incomplete. AIM: To evaluate the clinical presentation and the natural history of type I AIH. METHODS: Seventy-three consecutive patients with a regular follow-up of at least 2 years were prospectively included in the study. The mean follow-up was 91 +/- 61 months. RESULTS: Patients with 'acute' onset at presentation were significantly older than patients with 'chronic' onset (P < 0.05) and had significantly higher serum levels of transaminase, gamma-glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow-up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow-up, but seven patients were transplanted. The cumulative transplant-free probability of survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.

[Autoimmune hepatitis: present knowledge]. / Epatite autoimmune. Conoscenze attuali.

Autoimmune hepatitis (AIH) is a rare and chronic disease which may lead to liver cirrhosis if not correctly treated. Its etiology is unknown, but some progresses have been obtained in the knowledge of damage pathogenesis, its immune mechanisms and genetic predisposition (female gender, presence of HLA DR3 and HLA DR4). It seems that such predisposition favours some agents (e.g. drugs or viruses) to trigger the pathological process. Patients present with variable, often few and unspecific symptoms. Diagnosis is made on the basis of anamnestic (absence of other causes, such as virus infections or alcohol abuse), serological (autoantibodies, high levels of aminotransferases, hypergammaglobulinemia), and histological data (piecemeal necrosis further to bridging necrosis, panlobular and multilobular necrosis); these data are processed by a scoring system which is helpful for the diagnostic definition. Therapy is founded in immunosuppressor drugs, mainly steroids and azathioprine, but a lot of other drugs have been studies for cases of recurrence and of intolerance to the standard treatment.

Isozyme polymorphisms provide evidence of clinal variation with elevation in Nothofagus pumilio.

Variable physical conditions along elevational gradients strongly influence patterns of genetic differentiation in tree species. Here, the hypothesis is tested that different growth forms of Nothofagus pumilio, which characterizes the subalpine forests in the southern Andes, will display continuous genetic variation with elevation. At each of four elevational strips in three different mountain ranges, fresh leaf tissue was sampled from 30 randomly selected individuals to be analyzed by protein electrophoresis. Allelic frequencies were used to test for heterogeneity across populations and to classify populations into different elevational strips by discriminant analysis. The degree of population divergence was estimated by F(ST). Clinical variation on within-population genetic characteristics was analyzed by linear regressions against elevation. Seven enzyme systems coded for 14 putative isozyme loci, 57% of which were polymorphic in at least one population. Allele frequencies significantly varied with elevation and discriminant analysis separated populations at different elevational strips. Among-population divergence within any mountain range was small, but greater than among different mountain ranges. Overall, low-elevation populations were more variable than high-elevation populations, and regression analyses suggested continuous variation in populations of N. pumilio 100 m apart. Marked stepwise phenological differences on mountain slopes are most probably responsible for the isolation of nearby populations.

The esophageal chest pain. An update for clinicians.

Chest pain is a common symptom and even when there is evidence of only minor obstructive coronary artery disease on angiography, it leads to disability and imposes a substantial economic burden on health care system. Gastroesophageal reflux disease (GERD) and esophageal dysmotility disorders are thought to play an important role in the genesis of non-cardiac chest pain. Its pathogenetic mechanism remains unclear. The esophageal origin of the symptom may be identified by an aggressive trial of high-dose antisecretory drugs or an abnormal prolonged ambulatory pH monitoring study. Endoscopy is often normal and less useful in this population than in those with heartburn as presenting symptom. The use of manometry, with provocative testing to evaluate for esophageal motility abnormalities or esophageal sensitivity, allows optimal evaluation of those who do not have GERD. Patients with non-cardiac chest pain of unknown origin should be carefully screened for the occurrence of esophageal disorders but further research is needed to clarify the role of the latter on the pathogenesis of this symptom.

Genetic variation in the vulnerable and endemic Monkey Puzzle tree, detected using RAPDs.

Araucaria araucana (Monkey Puzzle), a southern South American tree species of exceptional cultural and economic importance, is of conservation concern owing to extensive historical clearance and current human pressures. Random amplified polymorphic DNA (RAPD) markers were used to characterise genetic heterogeneity within and among 13 populations of this species from throughout its natural range. Extensive genetic variability was detected and partitioned by analysis of molecular variance, with the majority of variation existing within populations (87.2%), but significant differentiation was recorded among populations (12.8%). Estimates of Shannon's genetic diversity and percent polymorphism were relatively high for all populations and provide no evidence for a major reduction in genetic diversity from historical events, such as glaciation. All pairwise genetic distance values derived from analysis of molecular variance (Phi(ST)) were significant when individual pairs of populations were compared. Although populations are geographically divided into Chilean Coastal, Chilean Andes and Argentinean regions, this grouping explained only 1.77% of the total variation. Within Andean groups there was evidence of a trend of genetic distance with increasing latitude, and clustering of populations across the Andes, suggesting postglacial migration routes from multiple refugia. Implications of these results for the conservation and use of the genetic resource of this species are discussed.

Effects of population disjunction on isozyme variation in the widespread Pilgerodendron uviferum.

Geographical range is considered a good predictor of the levels of isozyme variation in plants. Widespread species, often consisting of historically larger and more continuous populations, maintain higher polymorphism and are less affected by drift, which tends to erode genetic variation in more geographically restricted species. However, widespread species occurring in small and disjunct populations may not fit this pattern. In this study we examined genetic variation in Pilgerodendron uviferum, a conifer endemic to temperate forests of southern South America, and is such a widespread and habitat-restricted species. Twenty populations along the whole range of Pilgerodendron were analysed by isozyme electrophoresis to resolve 14 putative genetic loci. Eleven were polymorphic in at least one population although only six of them were polymorphic in more than one population. We found reduced within-population levels of isozyme variation, with only 11% polymorphic loci (0.95 criterion), 1.2 mean number of alleles per locus, and mean observed and expected heterozygosities of 0.024 and 0.033, respectively. Most genetic diversity was found within populations (H(T)=0.039, H(S)=0.033, F(ST) 15%). Greater polymorphism and lower divergence was estimated in the more geographically restricted and closely related Fitzroya. Thus, total range, in combination with information on the degree of among-population isolation, may be a better predictor of the levels of polymorphism than range size alone.

Doppler study of the uterine arteries and ovarian stroma in patients with polycystic ovary syndrome.

Doppler analysis of the uterine arteries and ovarian stroma was performed by transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and 22 ovulatory women. Vascularization of the ovarian stroma was more abundant in patients with PCOS than in control women, but no significant difference in the mean pulsatility index (PI) was observed between groups (1.14 +/- 0.28 for the PCOS group and 1.05 +/- 0.19 for the control group). The mean PI of the uterine arteries was significantly higher in the PCOS group (PI = 3.7 +/- 0.8) than in the control group (PI = 2.9 +/- 0.4). In the patients with PCOS, no correlation was observed between PI and luteinizing hormone, testosterone or androstenedione levels. Obesity had no effect on uterine artery PI, with no significant differences in this index when the 3 groups were subdivided into obese and non-obese groups.

[Variant syndromes in autoimmune hepatic diseases]. / Sindromi varianti nelle epatopatie autoimmuni.

Some autoimmune hepatic diseases patterns can be of difficult classification, sometimes as overlap of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and chronic viral hepatitis. The recognition of these forms is not so easy, but it is necessary for an effective therapeutic approach. At present, the specificity in these cases of the score system done and revised by the International Autoimmune Hepatitis Group is being discussed. Patients showing such diseases have different modalities of presentation of their hepatic disease and different courses. The role of histology appears to be important, but often the overlap of more manifestations is not helpful to a correct diagnostic definition. The variant syndromes could be classified as intermediate patterns of cholestatic forms and of autoimmune hepatic diseases or cholestatic forms of autoimmune hepatitis or hepatitic forms of cholestatic syndromes.

Genetic variation in Fitzroya cupressoides (alerce), a threatened South American conifer.

Fitzroya cupressoides (alerce, Cupressaceae) is a large and exceptionally long-lived conifer, endemic to a restricted area of southern Chile and neighbouring areas of Argentina. As a result of its high economic value, the species has been severely exploited for timber, and remnant populations are fragmented and often highly disturbed. The species is thought to have undergone a major range contraction during the last glaciation. In order to assess the extent of genetic variation using DNA markers within and between populations of this species, samples were obtained from throughout the natural range and analysed for random amplified polymorphic DNA (RAPD) variation. Eight 10-mer and three 15-mer primers were used to produce a total of 54 polymorphic bands. Shannon's diversity estimates were calculated to provide an estimate of the degree of variation within each population. Values varied from 0.343 to 0.636 with only the lowest value differing significantly from the others (Spop = 0.547). This indicated that there is a significant degree of variation within each population, and did not provide evidence for genetic 'bottle-neck' effects within the species. A pairwise distance measure calculated from the RAPD data was used as an input for principal coordinate (PCO) and AMOVA analyses. The first three principal coordinates of RAPD distances described 8.3, 5.9 and 5.4% of the total variance, respectively, and a degree of clustering of samples according to their geographical origin was detectable. AMOVA analysis indicated that although most of the variation (85.6%) was found within populations, a significant proportion (P < 0.002) was attributable to differences between populations. An UPGMA dendrogram constructed using phi ST values derived from AMOVA produced a pattern broadly similar to that produced by the PCO, highlighting differences between three main groups of populations within Chile: those from the northern Coastal Range, the southern Coastal Range and Central Depression, and the Andes. Populations from Argentina also emerged as significantly different from those in Chile. These results are interpreted in the context of the postglacial history of the species, and their implications for the development of conservation strategies for Fitzroya are discussed.

Minimax refining of wideband antireflection coatings for wide angular incidence.

The design of antireflection coatings at any light incidence is a challenging task in optics. To this aim, a minimax method is presented: it minimizes the maximum deviation of the spectral reflectance from the desired specifications over the wavelength for a given set of incidence angles. Refining is limited to lossless coatings with assigned refractive indices and undetermined thicknesses; the algorithm consists of iterating appropriate linear optimization steps. In the examples some minimax-refined coatings are compared with coatings reported in the literature.

Minimax refining of optical multilayer systems.

A new minimax method for refining optical multilayer systems is presented. It minimizes the maximum deviation of the spectral transmittance from the desired specifications. These are assigned in such a general way that any shape can be approximated. The algorithm consists of iterating optimization steps that are obtained by developing the transmittance in the Taylor expansion versus the known parameters and solved by piecewise-linear programming. The investigation is limited to the design of losslessmultilayers with assigned refractive indices and undetermined thicknesses. Some minimax-refined designs are compared favorably with those reported in the literature.

Continuation method for synthesizing antireflection coatings.

A continuation method for synthesizing antireflection multilayer coatings is presented. It takes into account the family of similar problems constituted by the syntheses of spectrally flat coatings that approximate different transmittance levels in the range 0-1. This method traces a path moving from the transmittance (in air) of the chosen substrate to the full transmittance. Whenever one or more thicknesses become too thin, this path is branched by investigating the existence of other local minima, so several optimal designs characterized by different numbers of layers are obtained. Some examples show the capabilities of the proposed synthesis.