Estimates of lifetime attributable risk of cancer after a single radiation exposure from 64-slice computed tomographic coronary angiography.

AIMS: To estimate the life attributable risk (LAR) of cancer incidence over a wide range of dose radiation exposure and a large spectrum of possible diagnostic computed tomographic coronary angiography (CTCA) scenarios. METHODS: This study included 561 consecutive patients who underwent a successful prospective ECG-gating CTCA protocol (low-dose group) 64-slice CTCA and 188 patients who underwent retrospective ECG-gating CTCA with ECG-triggered dose modulation CTCA (high-dose group). LAR was computed, given the organ equivalent dose, for all cancers in both sexes. LAR was tabulated for each decile of dose-length product by 10-year age classes, separately for each sex. RESULTS: Estimates of LAR of any cancer for an exposure at age < or =40 year were lower in males than in females for any given quantile. At age >/ or =50 years, LAR was similar between sexes only at the lowest exposure doses, whereas at higher dosage, it was, in general, higher for women. At the median age of this case series (62 years) and for a radiation exposure ranging from 1.33 to 3.81 mSv, LAR was 1 in 4329 (or 23.1 per 10(5) persons exposed) and 1 in 4629 (or 21.6 per 10(5) persons) in men and women, respectively. For an exposure ranging from 10.34 to 18.97 mSv at the same median age, the LAR of cancer incidence was 1 in 1336 (or 74.8 per 10(5) persons) in men and doubled (1 in 614 or 162.8 per 10(5) persons) in women. CONCLUSIONS: This study provided an estimate of the LAR of cancer in middle-aged patients of both sexes after a single diagnostic CTCA, providing an easy-to-read table.

Aspectos epidemiológicos da Leishmaniose Tegumentar Americana na região Noroeste do Estado do Paraná / Epidemiological aspects of American Cutaneous Leismaniasis in the northwest region of the state of Paraná

No Estado do Paraná, a primeira notificação de leishmaniose tegumentar americana ocorreu em 1917 e a partir de 1980 observou-se um aumento do número de casos, mantendo-se endêmica e acometendo pessoas de todas as faixas etárias e em ambos os sexos. Este estudo teve como objetivo realizar um levantamento epidemiológico sobre a ocorrência de LTA em pacientes atendidos no Laboratório de Ensino e Pesquisa em Análises Clínicas da Universidade Estadual de Maringá (LEPAC/UEM). Foi realizado um estudo retrospectivo e descritivo em base de dados secundário de 1986 a 2005, com 1656 pacientes segundo as variáveis: sexo, idade, ocupação, procedência, local de moradia, forma clínica e diagnóstico. A maioria dos pacientes era do sexo masculino (72,6%) e adquiriu a infecção no Estado do Paraná (97,8%), residia em área urbana (64,3%) dos quais 51,3% adquiriu a infecção durante atividades de lazer. O diagnóstico da maioria dos pacientes foi estabelecido nos dois primeiros meses de evolução das lesões (54,0%) e apresentando a forma cutânea da doença (88,9%). Uma parcela (34,4%) significativa dos pacientes que residiam em área rural adquiriu a infecção no domicílio ou peridomicílio. O estudo mostra a predominância da forma cutânea da leishmaniose tegumentar americana e sugere a atividade de lazer e o ambiente do domicilio como fatores preditivos importantes para a infecção.

The first notification of American cutaneous Leishmaniasis (LTA) in the state of Paraná, Brazil, occurred in 1917 and an increasing number of cases has been reported since 1980. This parasitic skin disease, spread by the bite of infected sandflies, is still an endemic problem, with recurrence in both sexes and in all age groups. The objective of this study was to perform a survey on the occurrence of American cutaneous Leishmaniasis in patients attended at the Teaching and Research Clinical Analysis laboratory at the State University of Maringá (LEPAC/UEM). A retrospective and descriptive study was carried out, based on secondary data (1986-2005) on 1656 patients, relating to their sex, age and occupation and the origin, clinical forms and positive diagnosis of the disease. Most of the patients were male (72.6%), lived in the urban area (64.3%) and acquired the infection during outdoor leisure activities (51.3%) in the State of Paraná (97.8%). The cutaneous form of the infection predominated (88.9%) and the diagnosis was made in the first two months of development of the lesions (54.0%). A significant part (34.4%) of the patients who lived in the rural area acquired the infection inside or close to their homes. The study shows the predominance of the cutaneous form of American cutaneous Leishmaniasis and suggests that leisure activity and housing conditions could be useful predictive factors for the infection.

Haemoglobin variants and anaemia among pre-school/school children in north-east Brazil.

In this study we investigated the presence of haemoglobin (Hb) variants and anaemia among 382 pre-school/school children from Bahia State, Brazil, a state where intermixing involving people from African origin is the highest in the country. Hb variants were investigated by cellulose acetate electrophoresis at alkaline pH. The pattern obtained was confirmed by citrate agar electrophoresis at pH 6.2. From the 382 children investigated, 79 (20.7%) had Hb variants: 47 (59.5%) had HbAS, 28 (35.4%) HbAC, 3 (3.8%) HbSC and 1 (1.3%) HbCC. Two hundred and fourteen children had anaemia. From these, 39 had microcytosis and 14 had low values of ferritin (<12 ng/ml). We cannot exclude thalassaemia among the children with microcytosis and hypochromia because it was not investigated. The majority of the children showed high mean values of ferritin, suggestive of subclinical infection. There was no difference when we compared the prevalence of anaemia among children with Hb variants (65.8%) and those without Hb variants (53.5%) (P = 0.06). These data demonstrate that Hb variants and anaemia are probably important public health problems in north-east Brazil.

Aphasia quality of life: reliability of the Italian version of SAQOL-39.

AIM: In recent times there has been an increasing interest in assessing the quality of life (QOL) in stroke clinical trials. To our knowledge, an Italian tool suitable for this purpose is still missing. So we adapted to Italian language the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39), that is a British questionnaire recently validated with aphasic subjects. The aim of this paper is to validate our version of SAQOL-39. METHODS: To determine the matching of our version, we requested a native English speaker to translate the Italian version into English. Twelve patients (7 male, 5 female; mean age 66.4 years) were submitted to our test. All subjects were interviewed twice by 2 raters, at 24 h of distance. Neither examinator knew results of the other interview. Statistical analysis was performed by determining Cronbach's a and the intraclass correlation coefficient (ICC). RESULTS: Comparing the original SAQOL-39 to the English translation of our Italian version, we found only a low percentage (10%) of minimal semantic variations. As for test-retest reliability, ICC for global score was 0.898 (ICC(2,39)). ICC range for SAQOL-39 subdomains was 0.816 to 0.969. Cronbach's a for full scale scores was 0.916 (subdomains ranged 0.767 to 0.976). Results seem good as for usefulness, reliability and acceptability of the Italian version of SAQOL-39, like the original version of this test. CONCLUSIONS: Our Italian version of SAQOL-39 seems suitable for clinical use. A multicentric study aiming to compare our data to original English ones is in progress.

Impact factor and electronic versions of biomedical scientific journals.

BACKGROUND AND OBJECTIVES: The development of electronic editions of scientific journals and the rapid spread of scientific information might modify the pattern the bibliographic citations, and thus the impact factor and quality of journals. We assessed changes in the impact factor over years of a number of journals and whether the presence of an electronic version of the journal was associated with the impact factor score. DESIGN AND METHODS: This is a retrospective longitudinal study. The availability of journals (table of contents (TOC), abstracts, full text and free full text) on Internet, in years 1995-2000, was assessed between December 2000 and January 2001. The first 20 top-journals from 8 subject categories were included. Changes in impact factor over time and association with Internet availability were modeled. RESULTS: Overall, 118/139 journals (85%) had their TOC on the Internet, of these 107 (77%) had abstracts, 97 (70%) had full text and 33 (24%) free full text. The median impact factor for all journals was 1.65, 2.08, 2.10, 2.21 and 2.35 for the years from 1995 to 1999, respectively. This increase was statistically significant, with differences among subject categories. The presence of TOC, abstracts and full text on the Internet was also significantly associated with higher impact factor, after accounting for time and subject category. INTERPRETATION AND CONCLUSIONS: The impact factor has been used for assessing the quality of journals. We identified a new limitation of this indicator: the impact factor seems to be related to the amount of circulation of information through Internet. This could be a temporary limitation, associated with diffusion of journals on, and spread of Internet.

Efficacy and safety of high dose intravenous ciprofloxacin in the treatment of bacterial pneumonia. Italian Ciprofloxacin Study Group.

One hundred and fifty three hospitalized patients were enrolled in an open, prospective, multi-center study on the efficacy and safety of intravenous ciprofloxacin (400 mg i.v., b.i.d.) for acute bacterial pneumonia: 93 (63%) patients were valid for efficacy out of 148 valid for intention-to-treat analysis. The most commonly isolated organisms from 93 valid-for-efficacy patients were Pseudomonas aeruginosa (17%), Haemophilus influenzae and parainfluenzae (17%), Streptococcus aureus (14%) and Streptococcus pneumoniae (11%). Cure was achieved in 89/93 (95.7%) valid-for-efficacy patients; effective eradications were obtained in 42 (45%) and presumed eradications in 48 (52%) of the 93 patients. Mild or moderate adverse events (AE) occurred in 13/153 (8.5%) patients assessable for safety; all but one AE were rapidly reversible and only one treatment-stop (0.65%) was decided. The treatment of acute bacterial pneumonias with high-dose parenteral ciprofloxacin appears to be efficacious and well tolerated.

The effect of heart rate on the slope and pressure half-time of the Doppler regurgitant velocity curve in aortic insufficiency.

The effect of the heart rate on the Doppler aortic regurgitant velocity curve was evaluated in 14 patients with aortic regurgitation. The heart rate was increased in two steps with either endocardial or transesophageal pacing in 12 patients and with atropine sulfate in 2 patients (increased from 66 +/- 7 to 82 +/- 4 beats per minute [step 1] to 100 beats per minute [step 2]) in all patients. The increased heart rate resulted in an increased regurgitant slope (from 3.3 +/- 1.2 to 4.5 +/- 1.7 m/s2 [step 1] to 5.8 +/- 1.9 m/s2 [step 2]; p < 0.01) and a shortened pressure half-time (PHT) (from 442 +/- 136 to 323 +/- 98 ms [step 1] to 254 +/- 69 ms [step 2]; p < 0.01). Such variations occurred in the presence of a prevalent hemodynamic improvement, noninvasively suggested by a decreased Doppler-derived left ventricular end-diastolic pressure (LVEDP) (from 23 +/- 10 to 14 +/- 10 mmHg at the highest heart rate; p < 0.05) and by an increased peak aortoventricular diastolic gradient (from 80 +/- 20 to 84 +/- 22 at the highest heart rate; p < 0.05). The PHT and slope correlated with diastolic time (r = 0.74 and -0.65, respectively; p < 0.001). The relative-PHT (PHT/diastolic time x 100) showed insignificant changes during the increase in heart rate and correlated better than the PTH with color Doppler assessment of regurgitation severity (r = -0.73; p = 0.003, and r = -0.53; p = 0.05, respectively). We concluded that the slope and PHT of the aortic regurgitant velocity curve were rate-dependent; the relative-PHT appeared to limit the influence of the heart rate on PHT.

[A measure of productivity in cardiology based on medical acts]. / Una misura di produttività in cardiologia basata sugli atti medici.

BACKGROUND: The decreased availability of economic resources, opposed to the increased demand for medical assistance, requires the use of methods to assess hospital efficiency. Purpose of our study was to evaluate and quantify the "products" of a cardiology department, as well as the changes in time of their production, by means of a catalogue of medical acts, set up for the French health system (CdAM). METHODS: The study includes the 224 admissions occurring in October 1987 and the 209 admissions of October 1992. Medical acts were recorded for all admissions, by number of acts as well as by weight of acts; this weight (expressed as complexity/cost index or ICR) takes into account the use of resources in terms of medical staff and nursing staff, together with technical resources, for each act. In 1987 and 1992, 1736 and 1603 acts were performed respectively, corresponding to a total weight of 24308 and 32194 ICR. RESULTS: The increased ICR appears to be related to an increase of invasive procedures, particularly of interventional electrophysiology and haemodynamics. By considering case mix, we observed an increment of ICR for the diagnosis of angina (from 194.3 to 227.4 ICR per patient), of arrhythmias (from 178.0 to 273.1) and of cardiomyopathy (from 95.6 to 179.7). CONCLUSIONS: In conclusion, CdAM allows to evaluate the cardiologic activity also in the Italian situation; the ICR of each act permits to estimate the human and technical burden, with subsequent easy internal and external comparisons.

[Double-blind placebo-controlled study of the effectiveness and tolerability of 10 and 30 mg ketorolac tromethamine suppositories in post-cholecystectomy pain]. / Studio in doppio cieco verso placebo sull'efficacia e la tollerabilità di ketorolac trometamina supposte da 10 e 30 mg nel dolore conseguente a colecistectomia.

OBJECTIVE: To evaluate the efficacy and tolerability of ketorolac tromethamine 10 mg and 30 mg suppositories in comparison to placebo, after single dose administration in patients suffering from post-operative pain after cholecystectomy. DESIGN: Double-blind, randomized, controlled study. SETTING: Anaesthesia Service. PATIENTS: 99 patients with severe pain following surgery. INTERVENTIONS: Cholecystectomy. MEASUREMENTS AND MAIN RESULTS: The analgesia activity of ketorolac tromethamine 10 mg and 30 mg suppositories were evaluated after single dose administration by assessing pain intensity and pain relief using a 4 point scale (VRS). At the end of the treatment period overall assessment of safety and efficacy were recorded by physician and patient. The results show that in both active groups after 30' and until 4 hours, pain intensity decreased significantly with respect to the baseline. However a statistically significant difference between groups of p < 0.02, p < 0.01 and p < 0.05 was found in favour of the 30 mg dose respectively at 30', 6 and 8 hours after administration. All the patients treated with placebo suppositories required another rescue analgesic drug and withdrew from the trial. Three patients complained adverse events not related to treatment: two on placebo and one on ketorolac 10 mg. The systemic and local tolerability of the drug was good. CONCLUSIONS: This study shows that ketorolac 30 mg suppositories are effective in clinical conditions, such as after surgery, in which pain control must be achieved within the shortest time interval and maintained or improved by means of a single route of administration.

p53 expression in human renal cell carcinoma: an immunohistochemical study and a literature outline of the cytogenetic characterization.

In this study both the incidence and pattern of p53 over-expression in various histological subtypes of a series of 36 cases of renal cell Grawitz carcinoma, partially studied in a previous paper, were analyzed. This series consisted of these histologic subtypes: clear cell non papillary (18 cases), clear cell papillary (2 cases), granular cell (5 cases), mixed (clear and granular cell) (9 cases) and spindle cell (2 cases). At present, our aim was, firstly, to see which were the best technical conditions for detection of p53 in the available paraffin-embedded tumor specimens, using several antibodies, specific for various epitopes; secondly, to investigate if some relation might exist between this expression and the histological features of these tumors. Twenty-five per cent (9/36 cases) resulted p53 immunoreactive, the highest percentage being represented in the papillary clear and granular cell carcinomas; low expression was detected in 11 cases (30%) and no reactivity in 16 cases (44%). Neither technical or dilution modifications proved to transform these latter results; however, detection was maximal using the CM-1 polyclonal rabbit antiserum. Thus, in RCC, expression of p53, analyzed in the light of the cytogenetic characterization through a literature review, resulted at low frequency. This finding means that mutation of the p53 gene are not frequent in the neoplastic transformation in RCC. Nevertheless, in spite of the small number of cases and of the short follow-up period of this study, detection of p53 positivity in tumors with either high grade and stage or high proliferative activity could suggest that p53 mutations lead to tumors of a more aggressive type.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between phosphorylation and cytochrome P450 destruction.

In our previous report we showed cytochrome b5 to be a competitive inhibitor of cAMP-dependent protein kinase (PKA) for interaction with cytochrome P450 (P450). While P450 was phosphorylated, cytochrome b5 was not. The phosphorylation of P450 resulted in an inhibition of its catalytic activity. In this report we attempt to determine the relationship between phosphorylation of P450 from phenobarbital-induced rat and its destruction. The results indicate there is a considerable alteration of P450 IIB1 when it is put into the phosphorylation medium. This includes destruction, i.e., loss of the hemoprotein nature (Soret peak), as well as denaturation, conversion of a proportion of the P450 to P420. The extent of phosphorylation correlated best with the amount of destroyed hemoprotein, and not with the formation of P420. There did not appear to be phosphorylation-dependent formation of apo-P450. Further, prior conversion of the P450 to P420 using sodium deoxycholate showed the same extent of phosphorylation as before the conversion. Thus, intact P450 is not required for phosphorylation nor is phosphorylation a prerequisite for hemoprotein destruction. P450 CAM (CIA1), which has the PKA substrate recognition sequence internalized, likewise undergoes conversion to P420 but this denaturation does not result in phosphorylation. Destruction of CIA1 with 6 M urea, however, did permit phosphorylation by PKA. P450 IIB1 destruction was greatly diminished by cytochrome b5. This stabilization resulted in a decreased degree of phosphorylation as well as an increase in negative ellipticity in circular dichroism, indicative of an increase in the proportion of alpha-helical content in the P450. Suggestions are made that this structural modification caused by cytochrome b5 stabilizes the P450 against denaturation as well as against destruction and phosphorylation. Further, when the P450 IIB1 was kept stable as P450 in the absence of cytochrome b5 and without loss of hemoprotein during the incubation period, using phosphate-glycerol buffer containing 0.4% Emulgen 911, the phosphorylation of the P450 was greatly diminished, with only minor effects on the protein kinase reaction itself. These results suggest that the protein kinase reaction itself. These results suggest that the protein kinase substrate recognition sequence is not readily accessible to PKA in mammalian P450 IIB1 but requires a destabilization of the protein for phosphorylation to take place.

Phosphorylation of cytochrome P450: regulation by cytochrome b5.

Rabbit liver cytochrome P450 LM2 and several forms of rat liver cytochrome P450 are phosphorylated by cAMP-dependent protein kinase (PKA) and by protein kinase C. Under aqueous assay conditions at neutral pH LM2 is phosphorylated only to a maximum extent of about 20 mol% by PKA. We show that detergents or alkaline pH greatly enhance the extent of phosphorylation of the cytochrome P450 substrates of cAMP-dependent protein kinase. In the presence of 0.05% Emulgen, PBRLM5, which appears to be the best cytochrome P450 substrate for cAMP-dependent protein kinase, incorporates phosphate up to about 84 mol% of enzyme. We reported previously (I. Jansson et al. (1987) Arch. Biochem. Biophys. 259, 441-448) that cytochrome b5 inhibits the phosphorylation of LM2 by cAMP-dependent protein kinase. In this paper, using PBRLM5, we demonstrate, by analysis of initial rates, that the inhibition of phosphorylation by cytochrome b5 is competitive, with a Ki = 0.48 microM. We also show that a number of forms of cytochrome P450 can be phosphorylated by protein kinase C, and that the phosphorylation of these forms by protein kinase C is also inhibited by cytochrome b5. These data suggest that the phosphorylation site(s) of cytochromes P450 may be located within or overlap the cytochrome b5 binding domain of the enzymes.

[HBV infection in hospital health workers: study conducted in a Piedmontese hospital]. / Infezione da HBV fra gli operatori sanitari ospedalieri: indagine condotta in un ospedale piemontese.

The screening for hepatitis B virus infection markers of 976 hospital employees pointed out that: the prevalence of subjects who are positive to at least one marker is relatively low (17.52%); the areas with higher rates of prevalence are: the infections diseases division and the radiological area; there is a statistically significant difference as for the positivity of one of the hepatitis B markers among the disaggregated non-medical staff for every single functional area. The data here collected are compared with those collected in other hospitals.

Experimental study on central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA).

The central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA) have been studied both in rabbits and in the guinea pig myoclonus model. This drug caused EEG synchronization and behavioural sedation both after intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in a dose-dependent manner, in rabbits. CEGABA showed a protective action against myoclonus induced by means of L-5-HTP in young guinea pigs. These data substantiate the hypothesis that CEGABA is a drug active on the central nervous system and probably exerts its action by strengthening cortical inhibition and/or directly acting on lower brainstem.

Identification of N-carboxyethyl gamma-aminobutyric acid in bovine brain and human cerebrospinal fluid.

The di-carboxylated derivative of spermidine, N-carboxyethyl gamma-aminobutyric acid (CEGABA) has been identified in bovine brain and human cerebrospinal fluid by HPLC. This discovery strongly suggests the existence of a metabolic pathway connecting polyamines and GABA via putreanine and CEGABA through progressive oxidative deamination of the amino terminal groups in spermidine.