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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 73 records · Page 4Linked to original sources

Effect of long-term losartan administration on renal haemodynamics and function in hypertensive patients.

In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.

Antihypertensive Agents↗

In vitro and in vivo effects of 2'-deoxycoformycin (Pentostatin) on tumour cells from human gammadelta+ T-cell malignancies.

Hepatosplenic gammadelta+ T-cell lymphoma represents a rare neoplasm of post-thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured mononuclear cells and purified gammadelta+ tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic gammadelta+ T-cell lymphoma. At a concentration of 10 microM, dCF, in the presence of 2'-deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on gammadelta+ tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3+/gammadelta+ tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3+/alphabeta+ lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3+/alphabeta+ T cells, which accounted, however, for only 20-25% of the initial cell input. Accordingly, the combination of dCF (10-100 microM) plus dAdo was able to induce a dose-dependent inhibition of clonogenic growth and [3H]-thymidine incorporation in purified CD3+/CD4-/CD8- gammadelta+ tumour cells. We also report that one patient with hepatosplenic gammadelta+ T-cell lymphoma in terminal leukaemic phase showed a striking haematological response to single-agent dCF given as fourth-line treatment. In particular, the selective clearance of gammadelta+ tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T-cell lymphoma.

Adenosine Deaminase Inhibitors↗

Prevalence of antibodies to Leptospira serovars in sheep and goats in Alto Adige-South Tyrol.

Serum samples from 313 sheep and 95 goats were collected during November 1993 in 26 localities in Alto Adige-South Tyrol and tested by microscopic agglutination test for antibodies to 28 serovars of the genus Leptospira. At the time of blood collection all the animals appeared healthy with no clinical sign suggestive of leptospirosis. The observed seroprevalence in sheep was 6.1%, whereas the seropositivity rate for goat serum samples was 2.1%. The highest serological prevalence in sheep was recorded for serovar castellonis, followed by poi, sejroe, hardjo subtype hardjobovis, copenhageni, and cynopteri. Titres to poi were the only ones found in goats. These findings, which are proof of Leptospira infection in Alto Adige-South Tyrol, indicate that foci of several serovars exist in this region.

Animals↗

Leiomyoma of the esophagus associated with bronchial obstruction owing to inflammatory pseudotumor in a child.

Although relatively common in adults, leiomyoma of the esophagus is a rare disorder in children. A single case report describes the coexistence of both esophageal and bronchial leiomyoma in a child. The authors describe the diagnostic and treatment challenges encountered in a 2-year-old boy with coexisting inflammatory pseudotumor and esophageal leiomyoma presenting as massive atelectasis.

Airway Obstruction↗

Delayed presentation of traumatic left-sided diaphragmatic avulsion. A case report.

We describe the case of a 35-year-old man who had suffered a severe multitrauma with blunt thoracic injury, left scapula and humerus fractures 5 years earlier. At the time of the trauma, a diaphragmatic lesion went unnoticed. Five years later, the patient had a 24-h history of increasingly severe abdominal pain with repeated vomiting. Helical CT showed a portion of the left hemidiaphragm avulsed from its insertions on the ribs with large-bowel loop obstruction herniated in the left hemithorax. The preoperative CT diagnosis was confirmed by surgery: reduction of the hernia and reinsertion of the hemidiaphragm to the lumbocostal arch were performed.

Adult↗

Effect of spironolactone and its metabolites on contractile property of isolated rat aorta rings.

Spironolactone and its active metabolites canrenone and potassium canrenoate are normally used as antihypertensive drugs. Although they are classified as antagonists of aldosterone, their mechanism of action cannot be ascribed solely to the regulation of ion transport in the distal tubule of nephrons. Here we have evaluated the effects of spironolactone, canrenone, and potassium canrenoate on contractile properties of isolated rat aorta rings. Spironolactone (1-300 microM), canrenone (1-300 microM), and potassium canrenoate (0.01-10 mM), in a concentration-dependent manner, relaxed rat aorta rings precontracted with phenylephrine (1 microM) or KCl (40 mM). These relaxant effects were not affected by prior treatment with either aldosterone (100 microM), glibenclamide (10 microM), or tetraethylammonium (10 mM), excluding the possibility that these drugs can be involved in either the nongenomic effect of aldosterone or on activation of potassium channels. Spironolactone and canrenone at concentrations of 30 and 100 microM, but not at 10 microM, and potassium canrenoate at concentrations of 0.3 and 1 mM, but not at 0.1 mM, significantly inhibited the phenylephrine (0.001-3 microM) concentration-response curve. Conversely, all tested concentrations of spironolactone (10, 30, and 100 microM), canrenone (10, 30, and 100 microM), and potassium canrenoate (0.1, 0.3, and 1 mM) significantly inhibited the concentration-response curve induced by cumulative concentrations of KCI (10-80 mM). Because both phenylephrine- and KCl-induced contractions imply an intracellular Ca2+ influx, we suggest that these drugs could act through an inhibition of voltage-dependent Ca2+ channels.

Animals↗

Normalizing complementary DNA by quantitative reverse transcriptase-polymerase chain reaction of beta2-microglobulin: molecular monitoring of minimal residual disease in acute promyelocytic leukemia.

Reverse transcription (RT)-polymerase chain reaction (PCR) raises unique methodological matters that may hamper the reliability of the procedure, especially when results should direct therapeutic decisions. One of these matters is represented by the RT step. The present study shows that differences in complementary DNA (cDNA) preparations purposely containing increasing amounts of retrotranscribed RNA were not disclosed by nonquantitative RT-PCR by two different housekeeping genes, leading to fictitious results when the expression of a given gene was quantitatively assessed. To overcome this problem, the following are proposed: 1) to evaluate the efficiency of RT step through the quantification, by competitive RT-PCR, of the expression levels of the housekeeping gene beta2-microglobulin (beta2M); 2) to normalize each cDNA preparation to be comprised within 1 standard deviation of the mean value of beta2M absolute level (3.14 +/- 1.14 attomoles/microg RNA) found by analyzing 33 cell lines of hematopoietic origin. To validate this strategy in a clinical setting, serial cDNA samples from patients were checked by conventional and quantitative RT-PCR for beta2M. Again, only a quantitative evaluation of beta2M levels was allowed to unveil significant differences, otherwise undetected, in the efficiency of RT reactions among these cDNA samples. Normalization of samples to obtain cDNA preparations containing comparable beta2M levels, eventually led to an increased sensitivity in the detection of PML-RARalpha fusion transcripts. This approach seems of great value for the monitoring of minimal residual disease in serial patient samples when a tumor-specific marker is available.

Actins↗

[The role of spiral computed tomography in sigmoid diverticulitis and the diagnostic-therapeutic implications].

PURPOSE: Colonic diverticula are saccules made of colonic mucosa and submucosa that herniate from the colonic lumen through the muscular layer of the wall where straight vessels penetrate. Diverticula are localized in the sigmoid colon in 95% of cases. Bacteria pooling in the lumen may cause lumen erosion and eventually perforation. CT is a useful technique in this condition because it can demonstrate intra- and/or extramural inflammation. Aim of this retrospective study was to assess the capabilities of contrast-enhanced helical Computed Tomography (CT) in sigmoid diverticulitis, especially relative to selection of the appropriate treatment. MATERIAL AND METHODS: We retrospectively reviewed the findings of 41 patients referred to our emergency department for diverticulitis. CT scans were performed 65 seconds after i.v. injection of nonionic contrast material (3 mL/s, 120 mL in all) administered by a CT-power injector. The following 7 CT findings were considered at least suggestive of acute diverticulitis: focal wall thickening, intramural abscess, inflammatory changes in the sigmoid mesentery root, pericolic fat inflammation or pericolic abscess formation, fistula, peritonitis. CT results were compared with surgical and physical findings. RESULTS: Based on CT findings, diverticulitis was classified as mild (25 patients) or severe (15 patients). In mild diverticulitis we found: focal sigmoid wall thickening (6 patients), intramural abscess (3 patients), sigmoid mesentery root thickening (5 patients), edema fluid (8 patients) and phlegmon (3 patients). In severe diverticulitis we found: sigmoid mesentery abscess (6 patients), fistula (5 patients) and peritonitis (4 patients). CT findings were questionable in 1 case and thus we could not exclude a perforated carcinoma. CONCLUSION: Contrast-enhanced helical CT is the imaging modality of choice in assessing mild or severe acute diverticulitis because it provides useful information for appropriate treatment planning in the emergency setting. This technique is most useful in questionable cases and in patients with suspected severe diverticulitis where a choice must be made between different treatment options.

Colon, Sigmoid↗

Severe Kawasaki disease in infants: two fatal cases.

Kawasaki disease is a systemic vasculitis that manifests itself in many ways. Infants may present as atypical cases and commonly experience severe inflammatory changes. The two cases that are presented here highlight unusual severity and pathology. Patient 1 was a three-month-old infant with atypical Kawasaki disease who developed gangrenous lesions, and coronary and extracoronary artery aneurysms. Multiorgan failure ensued with diffuse cardiac and extracardiac aneurysms and thromboses at autopsy. Patient 2 was a five-month-old infant with Kawasaki disease, cholangitis and peripheral gangrene. Severe coronary artery aneurysms developed and he died following a myocardial infarction, despite multiple doses of intravenous immunoglobulin, acetylsalicylic acid (ASA) and corticosteroids. There is a higher occurrence of atypical disease and more severe vasculitis in infants with Kawasaki disease. Pathological changes are described, including coronary and extracardiac lesions. Patient 1 shows extensive peripheral gangrene and widespread aneurysms, and patient 2 illustrates severe cardiac complications with diffuse organ inflammation. Therapies including intravenous immunoglobulin, ASA, corticosteroids and antithrombotics are reviewed.

Aneurysm↗

[Surgery in the cirrhotic patient. Prognosis and risk factors].

Patients with cirrhosis have reduced life expectancy. Surgery is often associated with clinical decompensation in this group of patients. The purpose of this paper is to study the surgical risk in cirrhotic patients undergoing nonderivative operations. Unfortunately, most of the studies in the literature about this problem are retrospective reviews with limitations. The conditions increasing surgical risk in cirrhotic patients are analysed. These include changes in the pharmacokinetics and pharmacodynamics of various drugs, altered hemostasis, poor resistance to infections, water retention, suture line insufficiency, chronic renal failure and congestive heart failure. Assessment of the disease stage in cirrhosis is very important, because the severity of hepatic abnormalities influences the prognosis. The Child-Pugh classification has been used extensively to risk-stratify patients with cirrhosis. However, the disregard for cardiorespiratory, renal, electrolyte balance and acid-base status limits its predictive accuracy. Recently a new scoring system, the Acute Physiology and Chronic Health Evaluation (APACHE III), has been introduced and seems to be superior to Child-Pugh for prognosticating short term survival of cirrhotic patients. In conclusion, surgery can be done safely only in cirrhotic patients with a good hepatic function. On the contrary, in patients with advanced cirrhosis, surgery causes a very high mortality. Finally, the patients with moderate hepatic failure can be operated only after a careful study of the disease and an adequate correction of the reversible risk factors.

Blood Coagulation↗

[Pharmaco-epidemiologic indicators for the analysis of drug consumption at the regional level].

The analysis of drug use is often limited to the description of per capita pharmaceutical expenditure. Differences that are observed in the comparison are attributable to the specific age and gender distribution of the compared populations, and to prescriptive behaviors of general practitioners. Aim of this paper is to analyze drug prescription in a local health unit of the Friuli-Venezia Giulia region. In order to take into account differences in age distribution among health districts we used "weighted" populations. An in depth analysis has been carried out on antihypertensive drugs to evaluate differences in GPs' prescriptive behavior. Both the differences among districts in the level of drug use, and variability observed in antihypertensive use in the population, suggest that drug prescription might be partly inappropriate.

Adolescent↗

Immunoblot and immunohistochemical comparison of murine monoclonal antibodies specific for the rat D1a and D1b dopamine receptor subtypes.

The two D1-like dopamine receptor subtypes, D1a and D1b, are structurally similar and pharmacologically indistinguishable using currently available ligands. To differentiate between the D1-like dopamine receptor subtypes, murine monoclonal antibodies to the rat Dla and the rat D1b dopamine receptor have been prepared. Rat D1-like and D2-like dopamine receptors expressed in Sf9 cells were used to verify the immunospecificity of the monoclonal anti-(D1a dopamine receptor) and anti-(D1b dopamine receptor) antibodies using immunoblot and immunohistochemical techniques. These two antibodies were used to compare the temporal dynamics of D1-like dopamine receptors expressed in Sf9 cells following infection with recombinant baculovirus and to monitor the partial purification of detergent solubilized receptors following ion exchange chromatography. Immunoreactivity of the anti-(D1a receptor) antibody was observed in the striatum and cortical regions of the rat brain using immunoblot techniques. No reactivity on immunoblots was observed for the anti-(D1b receptor) antibody using rat brain tissue, probably due to the low levels of receptor expression. For immunohistochemical studies using rat brain slices, the anti-(D1a receptor) antibody heterogeneously labeled cells and punctate processes within the striatal neuropil while labeling in the adjacent cerebral cortex was weak. Anti-(D1b receptor) antibody immunoreactivity was weak in the .striatum and generally limited to sparse perikarya in the dorsal region. However, immunoreactivity was observed in numerous cells within the vertical and horizontal limbs of the diagonal band and in the ventral pallidum. Immunoreactivity of the anti-(D1b receptor) antibody was also observed in layer V pyramidal neurons of the frontal sensorimotor cortex.

Animals↗

Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes.

BACKGROUND: The prognosis of patients with high risk myelodysplastic syndromes (MDS) (i.e., refractory anemia with excess of blasts [RAEB] and refractory anemia with excess of blasts in transformation [RAEB-t]) usually is poor. The combination of fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) (FLAG regimen) has been reported to be effective in patients with these diseases. METHODS: Forty-two patients (32 with RAEB-t and 10 with RAEB) were treated with the FLAG regimen. The median age was 61 years (range, 27-74 years). Forty patients were diagnosed with primary MDS and 2 patients had treatment-related MDS. Induction therapy was comprised of the FLAG regimen, whereas consolidation therapy included idarubicin and cytarabine. Patients with a compatible donor and who were age < 50 years were scheduled to undergo an allogeneic bone marrow transplantation (BMT), whereas for those patients without a donor and who were age < 60 years autologous BMT with peripheral blood stem cells mobilized by the consolidation regimen plus G-CSF was planned. RESULTS: Complete remission (CR) was achieved in 31 of 42 patients (74%; 95% confidence interval, 60-87%). Death during induction therapy occurred in 4 patients (9%) whereas 7 patients (17%) were resistant to the FLAG regimen. Toxicity from the consolidation regimen was negligible. All patients age < 50 years and achieving CR were eligible for allogeneic BMT procedures, with early recurrence being the only reason for exclusion. The median overall survival and disease free survival were 13 months and 18 months, respectively. Patients with favorable cytogenetics had a significantly better outcome compared with those patients with an adverse karyotype. CONCLUSIONS: The FLAG regimen is effective in patients with high risk MDS as well as in patients age > 60 years. The toxicity of the regimen is low and the majority of patients are eligible to undergo allogeneic BMT procedures after induction/consolidation therapy.

Aged↗

Reflex sympathetic dystrophy associated with amyotrophic lateral sclerosis.

Reflex sympathetic dystrophy (RSD) is a syndrome characterised by severe distal pain and vasomotor changes. It is believed to be caused by sympathetic nervous system overactivity. Trauma is the most frequent precipitant event. An association with amyotrophic lateral sclerosis (ALS) has been reported only once. We report three patients with ALS in whom the occurrence of RSD, in one of them at a very early clinical stage, seemed to have precipitated a more rapid clinical evolution. New sprouting re-innervating fibres have abnormal ion channels which might increase the risk of RSD. On the other hand, motor changes have been described in RSD, as well as motor strength improvement after RSD treatment. The complex relation of ALS with RSD is discussed. In all ALS patients pain followed by further loss of function should prompt a search for RSD.

Aged↗

Protease-activated receptor-2 involvement in hypotension in normal and endotoxemic rats in vivo.

BACKGROUND: The protease-activated receptor-2 (PAR-2) is expressed by vascular endothelial cells and upregulated by lipopolysaccharide (LPS) in vitro. PAR-2 is activated by a tethered ligand created after proteolytic cleavage by trypsin or experimentally by a synthetic agonist peptide (PAR-2AP) corresponding to the new amino terminus of the tethered ligand. METHODS AND RESULTS: Intravenous administration of PAR-2AP (0.1, 0.3, and 1 mg/kg) to rats caused a dose-dependent hypotension. A scrambled peptide was without effect. A specific trypsin inhibitor, biotin-SGKR-chloromethylketone, inhibited trypsin-induced hypotension but not that stimulated by PAR-2AP. In animals treated with LPS 20 hours earlier, we found an increased sensitivity to trypsin and PAR-2AP in the hypotensive response. In particular, PAR-2AP caused hypotension at a low concentration of 30 ng/kg. Moreover, PAR-2 was immunolocalized to endothelial and smooth muscle cells in aorta and jugular vein in LPS-treated rats, and increased levels of PAR-2 mRNA were shown by reverse transcription-polymerase chain reaction analysis. CONCLUSIONS: Our findings suggest that PAR-2 is important in the regulation of blood pressure in vivo. A functional upregulation of PAR-2 by LPS was demonstrated by the activity of concentrations of PAR-2AP that were inactive in normal animals. We conclude that PAR-2 may play an important role in the hypotension associated with endotoxic shock and may represent a new therapeutic target.

Animals↗