Population genetic implications from DNA polymorphism in random human genomic sequences

Denaturing high performance liquid chromatography (DHPLC) in combination with dye-terminator sequencing was used to survey 516 random genomic sequence tagged sites (STSs) for biallelic polymorphisms in 24 representatives of the major ethnic groups residing in the United States. Of the 301 polymorphic STSs (58.3%), 172 contained a single simple sequence polymorphism (SSP), while 78, 35, and 16 contained 2, 3, and 4-6 SSPs, respectively. Of the 541 SSPs identified, 342 (63%), 152 (28%), and 47 (9%) were transitions, transversions, and insertions or deletions, respectively. Only 21% of the STSs contained SSPs with a minor-allele frequency >20%. The nucleotide diversity estimate for random genomic sequences theta = 8.23 x 10(-4) was on average 50% higher than that for intragenic non-coding regions of the human genome ( theta = 5.52 x 10(-4). The discrepancy in Tajima's D statistic between 22 autosomal genes (D=-1.304+/-0.622, mean+/-SD) and random STSs (D=-0.27) suggests that, in the absence of significant mutation rate heterogeneity, the more negative values for genes are a consequence of directional selection rather than population growth.     

Outpatient Parenteral Antibiotic Therapy (OPAT): the Italian registry

In the early eighties, in the US the advantages (reduced costs, no hospitalisation trauma in children, no immobilization syndrome in elderly, reduction of nosocomial and acquired infections by multi-resistant organisms) of OPAT were identified and suitable therapeutic programs were established. Following the US experience, other countries set up their own OPAT programs which vary considerably from country to country because of different ways in which infections are managed in different parts of the world and because of different reimbursement systems. In order to understand the ways of managing OPAT and its results, a National OPAT Registry was set up in 1999 in Italy belonging to a wider International OPAT database, which collects data also from USA, Canada, Spain, Uruguay and Argentina. Up to now 396 patients and as many antibiotic courses have been included in the National Registry by eight different centres. The analysis of data permits to get information about the criteria of patient's selection, treatment (route of administration, site of care, choice of antibiotic, dosage and duration), outcomes and possible side-effects. Italian results offer a quite peculiar picture of OPAT in this country when comparing data with those of other countries. In contrast with other countries where soft tissue infections and osteomyelitis are the most frequent diagnoses for including patients in OPAT programmes, in Italy pneumonia and bronchitis are the top two amenable infections. Ceftriaxone, Teicoplanin and Amikacin are absolutely the top three antibiotics selected for OPAT in Italy which confirm that a single daily dose regimen represents a great advantage in terms of compliance. Finally, a large percentage of antibiotic courses (50%) are carried out by using the i.m. administration route, which is very unusual in other countries. OPAT Registry is still ongoing and it will give us more detailed information in the future about the management of infections in the outpatient setting, but it already permits to define an actual picture of OPAT in our country and/or to compare and correlate data and information from different countries.     

Locomotor behaviours and respiratory pattern of the Mediterranean fin whale (Balaenoptera physalus)

Twenty-four Mediterranean fin whales were tracked in open sea with a method based on the assessment of the animal differential position in respect of the observer's absolute position aboard a vessel, with the concomitant recording of the respiratory activity. Short distance video recording was also performed in two whales, permitting the simultaneous determination of single breath expiratory (T_E) and inspiratory (T_I) durations. In the 24 whales swimming at an average velocity of 1.39 (0.47) m·s^–1 [mean (SD), range: 0.62–2.44 m·s^–1], 2068 breaths organized in 477 respiratory cycles were observed. Each cycle entailed a prolonged apnoea dive phase [225 (91) s, T_dive) followed by a period near the surface [62 (28) s, surfacing], during which a series of breaths [4.6 (1.8)] was performed at short intervals. On the basis of track length and swimming velocity, two groups of animals were devised differing for convolution of the course (p<0.001), extension of ranging territory (p<0.01) and horizontal swimming velocity (p<0.05), which may represent two distinct behaviours. A possibly general mechanism of control of breathing in cetaceans was found, consistent with a model of constant tidal volume and variable respiratory frequency. Coherently with this model, T_E was independent of T_I or T_dive, in line with a passive expiration, while T_I appeared to be negatively correlated with T_dive (p<0.05), otherwise suggesting, similarly with terrestrial mammals, a significant role of hypercapnic stimulation. The estimated O₂ consumption of about 150 l·min^–1 is in line with the general allometric regression for mammals and corresponds to an energetic expenditure of 85–95 kJ·kg^–1·day^–1.Partially presented as a poster at The World Marine Mammal Science Conference and 12th Annual Conference of the European Cetacean Society, Monaco (Montecarlo), 20–24 January 1998.Angelo Colombini provided technical assistance.     

Stress influence on genesis,onset and maintenance of cardiovascular diseases: literature review

BACKGROUND: Recent mortality profiles in Brazil show that circulatory diseases are the leading cause of death in Brazil. These disorders contribute to 34% of deaths, with 50% of those deaths occurring in people under 50 years of age, that is, in people who are still active in the workforce. We assume that the growing incidence of cardiovascular diseases has occurred as the globalization of Brazil continues and brings with it the associated health risk factors of modern lifestyles, including stress. AIM: This paper reports the evidence on the influence of stress in the development, onset and progress of cardiovascular diseases. We aim to define the concept of stress and to point systematically to the interrelationships between its emotional and bodily manifestations through a discussion of the history and study of stress. We then suggest that factors leading to the experience of stress in Brazil are no different than in any other modern nation. We further offer a perspective on nursing interventions currently undertaken in Brazil in both hospital and community settings, with their more recent emphasis on health promotion and prevention. METHODS: An extensive literature review was undertaken. The data presented here were selected from reviews and clinical studies described in MEDLINE, LILACS, SciELO databases, as well as in the classical literature. We also refer to the current Brazilian literature on the prevalence of cardiovascular diseases and their associated risk factors. CONCLUSIONS: The incidence of cardiovascular diseases in Brazil is rising. Because of the globalization of Brazilian society, with its consequent competitiveness and accelerated modern lifestyles, Brazilians are no less immune to the usual health risk factors associated with cardiovascular diseases. Stresses associated with a modern lifestyle, however, are emerging as a new and major risk for developing cardiovascular diseases in Brazil.     

High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism

The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p<0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p<0.05 and p<0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p<0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.     

Alcohol abuse in social phobic patients: is there a bipolar connection?

BACKGROUND: Epidemiological and clinical studies have reported the frequent co-occurrence of social phobia (SP) and alcohol use disorders. Patients with SP often use alcohol to cope with the social situations they fear, and to lessen anticipatory anxiety, behavioral inhibition, and phobic avoidance. We investigated whether the presence of lifetime comorbidity with alcohol abuse was associated with significant differences as regards demographic and clinical features, family history and pattern of comorbidity in a large clinical sample of SP outpatients. METHOD: The sample comprised 153 outpatients who met DSM-III-R diagnostic criteria for SP. Demographic, family history and course characteristics were investigated by a semi-structured interview. Social phobic symptoms and the severity of the illness have been assessed by the Liebowitz Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). RESULTS: Thirty-four patients (22.2%) had a past or current history of alcohol abuse for at least 1 year. There were no significant differences between these patients and those without a history of alcohol abuse, as regards demographic features and lifetime comorbidity with major depression and other anxiety disorders. Bipolar disorder type II was found almost exclusively among patients with alcohol abuse, as well as family history for bipolar disorders. LIMITATIONS: Retrospective study. CONCLUSIONS: Our data indicate a strong relationship between bipolar II disorder and alcohol abuse comorbidity in patients with SP. The socializing and disinhibiting effect that many social phobics report might be mediated by mood elation induced by alcohol. The presence of bipolar diathesis in patients presenting with social anxiety might explain their increased susceptibility to alcohol, as they might undertake alcohol abuse as an attempt to overcome social difficulties.     

Symptomatic hypoglycemia in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia

BACKGROUND: Antimetabolite-based continuation therapy is commonly used for childhood acute lymphoblastic leukemia (ALL) and hypoglycemia after prolonged fasting has been recently reported. We have found that spontaneous, symptomatic hypoglycemia (SH) may also occur in such patients. PROCEDURE: Between 1995 and 1999, patients treated according to the AIEOP-ALL-95 study received BFM-type intensive chemotherapy; mercaptopurine (6-MP) was given (60 mg/m(2)/days, orally for 14 days) during the second part of induction and during consolidation therapy (25 mg/m(2)/day, orally for 8 weeks); thioguanine (6-TG) was given during reinduction therapy with protocol II (60 mg/m(2)/day, orally for 14 days); continuation therapy consisted of a combination of 6-MP (50 mg/m(2)/day orally) and methotrexate (MTX, 20 mg/m(2)/weekly, i.m.). We reviewed the charts of all patients treated for childhood ALL at our two centers. This was done to assess the incidence and the characteristics of all episodes of SH: sweating, pallor, nausea, abdominal pain with or without transient alterations of alertness, in the presence of blood glucose level of under 60 mg/dl. RESULTS: Six of 86 patients (6.9%) developed 18 episodes of SH. Five were male, none was older than 5 years, and four were only 3 years old. SH episodes occurred during consolidation (n = 2), reinduction (n = 7), and continuation (n = 9) phases. CONCLUSIONS: SH is a rare complication associated with administration of the purine analogues, mercaptopurine and thioguanine to children with reduced fat storage and young age.