[Use of estrogen-progestins in secondary prevention].
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Aged↗
Biomedical subjects
R Rossi
Publications and source records attributed to R Rossi.
[The diagnosis of ischemic cardiopathy in women].
Risk stratification and therefore evaluation of pre-test probability of coronary artery disease represent an important point in order to choose the ideal noninvasive test in women. Risk evaluation may be performed in relation to the presence of so-called major (hypertension, diabetes, age > 65 years) or minor (dyslipidemia, smoking abuse) risk factors. The standard ECG exercise test represents an important step, but only if easily interpretable and feasible: a complete negative test suggest the absence of coronary artery disease; its positivity should indicate the opportunity to perform coronary angiography in the presence of moderate to severe pre-test probability. If ECG exercise test is not feasible, we would suggest a test of imaging; in the case of high pre-test probability we would recommend a test with high specificity, such as echo-stress test, whereas in the case of lower pre-test probability we would prefer a test with high sensitivity, such as myocardial scintigraphy.
Chest Pain↗
[Cardiac rupture in thoracic trauma].
Thoracic trauma frequently involve damage to the cardiac structures and in the worst cases, the progressive degeneration and necrosis of the damaged tissue lead to cardiac rupture. The high mortality resulting from cardiac tamponade requires the prompt execution of diagnostic tests to provide as much useful information as rapidly as possible in order to start immediate therapy. A case of cardiac rupture manifested by the onset of atrial fibrillation in a patient admitted to Intensive Care after a car accident is described. The scarce significance of objective examination, the aspecific nature of chest X-ray and ECG alterations prompted the execution of a more thorough diagnosis. Transthoracic and transesophageal ultrasonography are both minimally invasive and highly specific: in a short time, not only did they confirm cardiac rupture, but they also focalised the site of the lesion, thus allowing a more targeted and rapid surgical approach. The relative frequency of cardiac lesions following closed thoracic trauma, the lack of incontrovertible signs and symptoms of late cardiac rupture, and the extreme severity of its clinical consequences argue in favour of using specific and sensitive diagnostic tests that can not only exclude or ascertain the presence of these lesions, but also allow subsequent serial controls aimed at diagnosing late cardiac ruptures.
Accidents, Traffic↗
Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria.
Retinol (vitamin A alcohol) is an accepted adjunctive treatment in infections such as measles. There is also indirect evidence from in vitro, animal and human studies that retinol supplementation may be beneficial in severe malaria. There have, however, been no studies that have examined the pharmacokinetics of acute retinol supplementation in severe illness. To establish whether mobilization of intramuscular retinyl palmitate (RP) and its availability as retinol are adequate in complicated falciparum malaria, we administered a single dose of 400000 i.u. of RP to six Vietnamese adults with severe malaria. Another 28 patients were not given RP. All patients had blood samples taken over 96 h for RP and retinol assay using HPLC, and received conventional anti-malarial and supportive therapy. Admission serum retinol concentrations were below the lower limit of the reference range (<1.0 micromol/l) in 74% of the 34 patients. In supplemented patients, analysis of serum RP between 0 and 96 h using a multi-compartmental model revealed a median (range) delay in mobilization of 6.9 h (0.7-15.1 h), a bioavailability of 55% (19-100%) and an elimination half-life of 13.5 h (4.2-23.7 h). The area under the serum retinol curve expressed as an absolute or percentage change from baseline was greater in supplemented than in unsupplemented patients (P<0.05). The separation in median serum retinol concentrations in the two groups was maximal at 48 h. The model-derived retinol half-life [1.5 (0.7-15.8) h] suggested rapid uptake, metabolism and/or excretion. In conclusion, there is variable RP bioavailability in severe malaria, but a significant if delayed increase in serum retinol over that associated with recovery from the infection. In severe infections, RP supplementation appears simple, well tolerated and of potential benefit once anti-microbial and supportive therapy have been established.
Adult↗
[Registry of genetic and malformative diseases in the province of Macerata].
OBJECTIVES: The aim of this epidemiological research is to evaluate the prevalence of genetic diseases and malformative syndromes in paediatric population living in the Macerata county. MATERIAL AND METHODS: All the data were collected through a careful analysis of a specific questionnaire sent to all the family paediatricians. RESULTS: 23,379 children living in Macerata county, aged 0 to 9 years, were evaluated (93.8% of all this paediatric population). Among those were found N 400 cases of genetic diseases and malformative syndromes: Malformations Tot.N. 255 cases (63.3% of the reported cases); Malformative Syndromes Tot. N. 55 cases (27.8% of the reported cases); Endocrinology and Metabolic Diseases Tot. N. 41 cases (10.3% of the reported cases); Osteochondrodysplasia Tot. N. 22 cases (5.7% of the reported cases); Other Tot. N. 28 cases (7.0% of the reported cases); Male population was found more affected than female: M/F ratio = 1.4. The analysis of the data showed an increasing trend in detecting these pathological conditions, consistent with the increase in geographic altitude (3 areas considered): 0-100 meter = 0.88%; 100-600 m.a.s. = 1.34%; over 600 m.a.s. = 1.88%. CONCLUSION: The knowledge of the number of children affected by genetic and malformative diseases in the Macerata county is relevant in order to establish a Genetic Service with the aim to better support the medical assistance of these patients and counselling service for the families.
Child↗
The replication factory targeting sequence/PCNA-binding site is required in G(1) to control the phosphorylation status of DNA ligase I.
The recruitment of DNA ligase I to replication foci in S phase depends on a replication factory targeting sequence that also mediates the interaction with proliferating cell nuclear antigen (PCNA) in vitro. By exploiting a monoclonal antibody directed at a phospho-epitope, we demonstrate that Ser66 of DNA ligase I, which is part of a strong CKII consensus site, is phosphorylated in a cell cycle-dependent manner. After dephosphorylation in early G(1), the level of Ser66 phosphorylation is minimal in G(1), increases progressively in S and peaks in G(2)/M phase. The analysis of epitope-tagged DNA ligase I mutants demonstrates that dephosphorylation of Ser66 requires both the nuclear localization and the PCNA-binding site of the enzyme. Finally, we show that DNA ligase I and PCNA interact in vivo in G(1) and S phase but not in G(2)/M. We propose that dephosphorylation of Ser66 is part of a novel control mechanism to establish the pre-replicative form of DNA ligase I.
3T3 Cells↗
Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics.
The use of cell culture models, based on human cell lines derived from the intestinal epithelium, is a promising new tool for the in vitro study of oral absorption of drugs. An assay has been developed using the Caco-2 cell line with the aim of studying the in vitro permeability of antibiotics. The reproducibility of the assay conditions have been assessed by means of the transport of two different marker molecules: 3H-mannitol and fluorescein, and transepithelial electrical resistance (TEER) value for cells monolayers. The results show that cells after 21 days of culture give significantly tighter monolayers than those after 15 days with higher reproducibility. Apparent permeability coefficients (Papp) have been measured for 13 antibiotics, known to be absorbed at different rates in humans. Papp values span from 0.18 x 10(-6) cm/s for cephaloridine to 5.79 x 10(-6) cm/s for rifampicin where the corresponding bioavailability values, known from literature, span from < 3 to 98%. A Caco-2 in vitro model appears to be suitable to investigate the transport of drugs across the intestinal epithelium. This model gives no information about the metabolic phase that follows the absorption of a drug but could provide information to investigate its pharmacokinetical behavior.
Anti-Bacterial Agents↗
Fluoro-Gold: An alternative viability stain for multicolor flow cytometric analysis.
BACKGROUND: The viability stains propidium iodide (PI) and 7-amino-actinomycin D (7-AAD) are excited at 488 nm, as are the commonly used antibody conjugates fluorescein isothiocyanate (FITC), phycoerythrin (PE), and cyanine 5 dye covalently coupled to R-phycoerythrin (RPE-Cy5). When excited by a single laser, spectral overlap in the emission of PI and 7-AAD with RPE-Cy5 precludes the use of these viability stains for three-color immunophenotyping, particularly when evaluating low levels of marker expression in viable target cells. The ultraviolet excitable dye hydroxystilbamidine methanesulfonate (Fluoro-Gold, or FG) binds to DNA at the A-T-rich regions of the minor groove in permeabilized or dead cells. We assessed the suitability of this dye as a viability stain. METHODS: The ability of FG to detect nonviable cells in fresh and cryopreserved human apheresed peripheral blood cells was compared with that of PI and 7-AAD. The stability of FG staining and the effects of dye and cell concentration on the discrimination of nonviable cells was determined by measuring changes in the median fluorescence of viable and nonviable cells. RESULTS: FG labeling at dye concentrations of 2-8 microM is stable for at least 3 h over a wide range of cell concentrations (4 x 10(5) to 4 x 10(7) cells/ml). Costaining studies and linear regression analysis show that cell viability as determined by FG is strongly correlated with estimates using PI (r = 0.9636) and 7-AAD (r = 0.9879). CONCLUSIONS: FG is a reliable, alternative viability stain that can be used in conjunction with fluorochromes including FITC, PE, and RPE-Cy5 for multicolor analysis using dual-laser instruments.
Antigens, CD↗
Altered multidrug resistance phenotype caused by anthracycline analogues and cytosine arabinoside in myeloid leukemia.
The expression of P-glycoprotein (Pgp) is often increased in acute myeloid leukemia (AML). However, little is known of the regulation of Pgp expression by cytotoxics in AML. We examined whether Pgp expression and function in leukemic blasts was altered after a short exposure to cytotoxics. Blasts were isolated from 19 patients with AML (15 patients) or chronic myeloid leukemia in blastic transformation (BT-CML, 4 patients). Pgp expression and function were analyzed by flow cytometric analysis of MRK 16 binding and Rhodamine 123 retention, respectively. At equitoxic concentrations, ex vivo exposure for 16 hours to the anthracyclines epirubicin (EPI), daunomycin (DAU), idarubicin (IDA), or MX2 or the nucleoside analogue cytosine arabinoside (AraC) differentially upregulated MDR1/Pgp expression in Pgp-negative and Pgp-positive blast cells. In Pgp-negative blasts, all four anthracyclines and AraC significantly increased Pgp expression (P =.01) and Pgp function (P =.03). In contrast, MX2, DAU, and AraC were the most potent in inducing Pgp expression and function in Pgp positive blasts (P <.05). A good correlation between increased Pgp expression and function was observed in Pgp-negative (r =.90, P =.0001) and Pgp-positive blasts (r =.77, P =.0002). This increase in Pgp expression and function was inhibited by the addition of 1 micromol/L PSC 833 to blast cells at the time of their exposure to these cytotoxics. In 1 patient with AML, an increase in Pgp levels was observed in vivo at 4 and 16 hours after the administration of standard chemotherapy with DAU/AraC. Upregulation of Pgp expression was also demonstrated ex vivo in blasts harvested from this patient before the commencement of treatment. In 3 other cases (1 patient with AML and 2 with BT-CML) in which blasts were Pgp negative at the time of initial clinical presentation, serial samples at 1 to 5 months after chemotherapy showed the presence of Pgp-positive blasts. All 3 patients had refractory disease. Interestingly, in all 3 cases, upregulation of Pgp by cytotoxics was demonstrated ex vivo in blasts harvested at the time of presentation. These data suggest that upregulation of the MDR1 gene may represent a normal response of leukemic cells to cytotoxic stress and may contribute to clinical drug resistance.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Preferential transport of glutathione versus glutathione disulfide in rat liver microsomal vesicles.
A bi-directional, saturable transport of glutathione (GSH) was found in rat liver microsomal vesicles. GSH transport could be inhibited by the anion transport blockers flufenamic acid and 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid. A part of GSH taken up by the vesicles was metabolized to glutathione disulfide (GSSG) in the lumen. Microsomal membrane was virtually nonpermeable toward GSSG; accordingly, GSSG generated in the microsomal lumen could hardly exit. Therefore, GSH transport, contrary to previous assumptions, is preferred in the endoplasmic reticulum, and GSSG entrapped and accumulated in the lumen creates the oxidized state of its redox buffer.
Alamethicin↗
An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies.
BACKGROUND: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examined the feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (Taxol) and radiation therapy. METHODS: Fourteen patients with a median age of 56 years (range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m2 concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated. RESULTS: Median follow-up from the initiation of treatment is 40 months (range 23-48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrostomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week. CONCLUSION: Paclitaxel can be given on a 3-week schedule at 100 mg/m2 concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites.
Adult↗
Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75 patients.
PURPOSE: This study was performed to describe prospectively the development and prognosis of severe ifosfamide-induced nephrotoxicity and to define the period of recommended renal follow-up after ifosfamide chemotherapy. PATIENTS AND METHODS: Renal function was followed in 75 patients after cessation of chemotherapy starting within the first year off therapy; median follow-up time was 31 months. The glomerular filtration rate was estimated by using the Schwartz formula. Proximal tubular transport capacities were evaluated for amino acids, phosphate, sodium, and glucose. In addition, serum bicarbonate level and alkaline phosphatase were measured. RESULTS: Five patients developed renal Fanconi syndrome during follow-up, and another seven patients developed a generalized subclinical tubulopathy. The latter condition always preceded Fanconi syndrome. Severe impairment of amino acid and phosphate reabsorption was seen in 28% and 17.3% of patients, respectively. Reductions in amino acid reabsorption preceded impairment of phosphate reabsorption. In patients with early impairment of phosphate reabsorption, renal prognosis was poor, whereas normal or only mildly impaired amino acid handling virtually excluded progressive tubular damage. CONCLUSIONS: Ifosfamide-induced renal tubular damage is a potentially progressive disease. Along with measurement of phosphate reabsorption, additional assessment of tubular amino acid handling is suggested, because it allows early discrimination of poor from favorable renal outcomes.
Adolescent↗
AlphaANP, AVP, and pituitary-thyroid axis in patients with congestive heart failure and acute respiratory failure.
The pituitary-thyroid axis and neurohumoral activation indexes were simultaneously investigated in 16 in-patients hospitalized for cardiac heart failure (CHF), New York Heart Association (NYHA), class II-IV, and Killip clinical scale, class II-III, to evaluate their relationship with CHF morbidity and the relative prognostic value. At entry the patients were divided into two subgroups (A and B), according to the severity of CHF. Patients were further classified into two subgroups, according to the subsequent clinical course (C, poor outcome and D, improved clinical course). Blood samples were obtained every day for the radioimmunoassay measurement of plasma alpha-atrial natriuretic peptide (alphaANP), arginine vasopressin (AVP), and thyroid hormones, and the results were compared with those of 12 control subjects. At admission, alphaANP and 3,3',5'-triiodothyronine (rT3) values were higher, while 3,3',5-triiodothyronine (T3) to rT3 (T3/rT3) ratio was lower in subgroups A and B than in controls (p<0.001), respectively, and in C than in D (p<0.001), respectively, according to the prognosis. Conversely, no differences in other thyroid indexes, nor a significant correlation between alphaANP and either rT3 or T3/rT3 ratio were present in any of the subgroups. AVP plasma levels in subgroup A were not statistically different from those of controls, whereas they were significantly decreased in subgroups B and C (p<0.05) and D (p<0.001). In conclusion, these results indicate that in CHF the pituitary-thyroid axis is not altered, that alphaANP and T3/rT3 ratio are non-invasive and reliable predictors of severity and prognosis, while AVP might be affected by the different pathological processes leading to CHF or by the concomitant use of drugs.
Acute Disease↗
Renal involvement in children with malignancies.
Renal complications in children with malignancies primarily arise from renal parenchymal tumors, "tumor lysis syndrome," and malignant infiltration or obstruction of the urinary tract. Therapy-associated renal side effects may develop following surgical and cytostatic treatment or be induced by radiotherapy. Clinically, both acute renal failure, for example following cisplatin, or chronic dysfunction, following ifosfamide and resulting in growth failure, are observed. Frequencies of renal impairment in these patients are, however, not well established, but terminal renal failure is a rare event: pediatric malignancies account for only 0.9% of patients on renal replacement therapy; the majority of these patients had been treated for a bilateral nephroblastoma. Since potentially serious long-term renal sequelae may evolve following both single measures and additive nephrotoxic effects, long-term monitoring of growth, blood pressure, and renal function is mandatory for a great proportion of former pediatric oncology patients. Future research should prospectively address frequencies of long-term renal impairment in these patients and should establish the prognosis of renal dysfunction. Only these data will ultimately allow risk-adopted use of potentially nephrotoxic treatment modalities and adequate counselling of patients.
Antineoplastic Agents↗
Chronic neuroborreliosis in infancy.
Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%-50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
Adolescent↗
Effect of the H1-histamine receptor agonist betahistine on drinking and eating behavior in pygmy goats.
The effect of different doses of the H1-receptor agonist betahistine (0.9 and 2, 4 and 8 mg/kg b.wt.(0.75)) on water and food intake was investigated in 12 pygmy goats. Intraperitoneal (i.p.) injection of betahistine (2, 4, and 8 mg/kg b.wt.(0.75)) stimulated drinking in a dose-dependent manner. Food intake was decreased after the injection of 4 or 8 mg/kg b.wt.(0.75) betahistine, respectively. The increase in water intake was characterized by an increased draft size and decreased latency to drink. The decrease in food intake at the highest dose tested was characterized by an increased latency to eat and by a decreased meal frequency, and food intake associated to drinking was decreased. In line with previous studies, these results support the hypothesis that food-associated drinking is mediated by stimulation of H1-receptors of histamine in pygmy goats.
Animals↗
Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women.
We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of the cardiovascular risk profile in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 200 postmenopausal women with mild to moderate hypertension. Patients received 17beta-estradiol (50 microg/day, transdermal) and norethisterone acetate (2.5 mg/ day, orally) or placebo. At baseline serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and fibrinogen plasma levels were measured and all subjects underwent complete M-mode and 2-D echocardiograms, which were repeated after 6, 12, and 18 months of hormonal replacement therapy. Compared with placebo, all values decreased significantly except for HDL cholesterol. In both groups, no modifications were observed in echocardiographic parameters, except for left ventricular mean diastolic and systolic wall thickness and left ventricular mass index, which showed a significant decrease in both groups. The reduction was greater in the treated group; the percentage of patients with left ventricular hypertrophy was 46% before randomization and 17.2% after 18 months of treatment (P < .0001), whereas in group II the percentage was 48% at baseline and 31.5% after 18 months (P < .05). In conclusion, transdermal 17beta-estradiol, associated with antihypertensive therapy, may contribute to the reduction of cardiovascular risk profile in hypertensive postmenopausal women.
Administration, Cutaneous↗
Specific contributions of various muscle fibre types to human muscle performance: an in vitro study.
Human skeletal muscle fibres can be divided in five groups: 1, 1-2A, 2A, 2A-2B and 2B, by using myosin heavy chain (MHC) isoforms as molecular markers. This study aimed to define the contribution of each fibre type to the contractile performance of human muscles. Single fibre segments were dissected from bioptic samples of vastus lateralis and chemically skinned. Force-velocity properties, including isometric tension (P0), maximal shortening velocity (Vmax), maximum power output (Wmax) and the velocity at which Wmax is reached (Vopt), were determined at maximum calcium activation. Among these parameters Wmax showed the largest range of variation: about nine times between 2B and slow fibres. Vopt also showed large (about four times) and significant variations between fibre types. Force development at submaximum calcium activation was studied and force-pCa curves were obtained for each fibre type. Calcium sensitivity was greater in 2B than in 2A and in slow fibres. The slope of the force-pCa curve was greater in fast than in slow fibres. At the end of the experiment the MHC isoform composition of each fibre segment was determined by gel electrophoresis. The functional properties of each fibre type are discussed in the light of the motor unit recruitment mechanism to understand their possible physiological role.
Biomechanical Phenomena↗