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Biomedical subjects

Antonio Pinto

Publications and source records attributed to Antonio Pinto.

At least 19 recordsLinked to original sources

Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.

Uncovering the role of upstream open reading frames (uORFs) challenges conventional views of one protein per messenger RNA and reveals the capacity of some uORFs to encode microproteins that contribute to cellular biology and physiology. This study explores the functional role of a recently identified mitochondrial microprotein, SLC35A4-MP, in the brown adipose tissue of mice. Our findings reveal dynamic regulation of SLC35A4-MP expression during primary brown adipocyte differentiation in vitro and during cold exposure or high-fat diet (HFD)-induced obesity in mice. Using a knockout mouse model, we show that loss of SLC35A4-MP disrupts mitochondrial lipid composition, decreasing cardiolipins and phosphatidylethanolamine in brown adipose tissue from HFD-fed mice. SLC35A4-MP deficiency also impairs mitochondrial activity, alters mitochondrial number and morphology, and promotes inflammation. Knockout mice accumulate acylcarnitines during cold exposure, indicating defective fatty acid oxidation. These findings reveal SLC35A4-MP as a previously unrecognized microprotein in regulating mitochondrial function and tissue lipid metabolism, adding to the growing list of functional endogenous microproteins.

Animals↗

Esophageal injuries: spectrum of multidetector row CT findings.

BACKGROUND: Aim of this study is to illustrate the multidetector row computed tomographic findings related to oesophageal injuries and their significance for therapeutic decisions. METHOD: From April 2002 to April 2005 we studied 16 patients with suspected oesophageal injury. Ten patients underwent standard chest radiograph, while five patients with suspected foreign body ingestion were submitted to cervical plain film and gastrografin swallow study. All 16 patients underwent multidetector row CT examination. RESULTS: In six patients with cervical, thoracic and abdominal trauma, CT showed the presence of thoracic traumatic lesions and findings suggestive of perforation of the oesophagus. In five patients with foreign body ingestion cervical radiography was positive in only one case, while CT showed the presence of a foreign body in all cases. In three patients with post-intubation complications, CT showed the presence of perioesophageal fluid collection containing small gas bubbles in two cases and an oesophageal-aortic fistula in one case. In the remaining two patients with suspected spontaneous oesophageal perforation, CT demonstrated an oesophageal wall oedema and thickening in one case, and oesophageal fluid distension with perioesophageal small bubbles gas and fluid in the second case. CONCLUSION: Oesophageal injuries, when complicated with perforation, constitute a life-threatening condition. Knowledge of the CT signs of oesophageal injuries has important implications for the role of imaging at the time of initial diagnosis.

Adult↗

Clinical, mammographic and ultrasonographic features of blunt breast trauma.

Evaluation of acute breast injury depends largely on the findings at physical examination. Patients may not initially remember the traumatic event to the breast, and mammography may be the first radiographic study to suggest this history, particularly if it shows findings of fat necrosis. Clinical, mammographic and sonographic findings resulting from non-iatrogenic trauma to the breast can be mistaken for signs of malignancy, especially because trauma often is not considered as a cause for such findings. In this paper some of the manifestations of blunt traumatic injury to the breast are presented. Familiarity with mammographic and sonographic findings of breast trauma is essential for the radiologist to avoid unnecessary biopsy and to avoid overlooking breast cancer.

Breast↗

Acute tracheobronchial injuries: Impact of imaging on diagnosis and management implications.

PURPOSE: To evaluate the role of chest radiography, single-slice CT and 16-row MDCT in the direct evidence of tracheobronchial injuries. METHODS: Patients with acute tracheobronchial injury were identified from the registry of our level 1 trauma center during a 5-year period ending July 2005. Findings at chest radiograph and CT were compared to those shown at bronchoscopy. RESULTS: Eighteen patients with tracheobronchial injury - three patients with cervical trachea injury, eight with thoracic trachea injury and seven with bronchial injury - were identified. Twelve patients had a blunt trauma (67%), six patients had a penetrating (iatrogenic) injury (33%). Chest radiograph directly identified the site of tracheal injury in four cases, showing overdistension of the endotracheal cuff in three cases and displacement of the endotracheal tube in one case. At the level of the bronchi, chest radiograph demonstrated only one injury. CT directly identified the site of tracheal injury in all the cases showing the overdistension of the endotracheal cuff at the level of the thoracic trachea (three cases), posterior herniation of the endotracheal cuff at the thoracic trachea (three cases), lateral endotracheal cuff herniation at the thoracic trachea (one case), tracheal wall discontinuity at the cervical (one case) and at the thoracic trachea (one case) and displacement of endotracheal tube at the cervical trachea (two cases). At the level of the bronchi, CT correctly showed the site of injury in six case including: discontinuity of the left main bronchial wall (two cases), the "fallen lung" sign (one case), right main bronchial wall enlargement (one case), discontinuity of the right middle bronchial wall (two cases). In one case, CT showed just direct "air leak" at the level of the carina suggesting main bronchus injury. This finding was confirmed by bronchoscopy. CONCLUSION: Chest radiograph was helpful for the assessment of iatrogenic tracheal injuries. CT detected the site of blunt tracheobronchial injuries in 94% of the cases. Multiplanar 16-row MDCT reconstructions, were essential for the optimal surgical approach.

Bronchi↗

Role of multidetector row computed tomography in the assessment of adrenal gland injuries.

OBJECTIVE: To determine the prevalence of adrenal injuries in a group of patients submitted to multidetector row CT evaluation after blunt trauma and to assess the impact of CT findings on clinical management decisions. MATERIALS AND METHOD: During a 4-year period, 2026 emergency CT examinations were performed in the setting of major blunt trauma. A total of 82 patients were retrospectively identified as having adrenal gland traumatic lesions. At multidetector row CT the following findings were considered specific of adrenal injury: round or oval hematoma expanding the adrenal gland, irregular hemorrhage obliterating the gland, uniform adrenal gland swelling, active extravasation of contrast material from the adrenal vessels and adrenal gland rupture. Associated CT findings were: stranding of the periadrenal fat, diffuse hemorrhage in the adjacent retroperitoneum and compression of the adrenal gland by adjacent traumatic lesions. RESULTS: We identified 82 patients (46 males and 36 females, age ranging from 15 to 86 years) with adrenal injuries. The right adrenal gland was injured in 60/82 patients, while the left adrenal gland was injured in 21 cases; in 1 patient bilateral adrenal gland traumatic lesions occurred. In 76 patients with non-isolated adrenal injuries concomitant injuries to the liver (49 cases), ipsilateral kidney (18 cases) and spleen (9 cases) were observed. Round or oval hematoma expanding the adrenal gland (61 cases), irregular hemorrhage obliterating the gland (14 cases), stranding of the periadrenal fat (9 cases) and diffuse hemorrhage in the adjacent retroperitoneum (8 cases) were the more frequent findings detected at CT. Six patients underwent surgical intervention for the presence of major injuries to the spleen (three cases), to the liver (one), to the right kidney (one), to the left kidney (one). Seventy-six patients were conservatively treated. CONCLUSION: Blunt adrenal injuries typically present as part of a multiorgan trauma. Familiarity with characteristic CT findings of adrenal trauma is essential for the radiologist to avoid misdiagnosis.

Abdominal Injuries↗

Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia.

The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical characteristics, pathologic features, and cytogenetic abnormalities. This heterogeneity is a challenge for evaluating response to treatment. Therapeutic trials in MDS have used various criteria to assess results, making cross-study comparisons problematic. In 2000, an International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS. These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life. The relevance of the response criteria has now been validated prospectively in MDS clinical trials, and they have gained acceptance in research studies and in clinical practice. Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria.

Humans↗

Do childhood diseases affect NHL and HL risk? A case-control study from northern and southern Italy.

To investigate the association between non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and exposure to childhood diseases, we analyzed an Italian case-control study that included 225 histologically-confirmed incident cases of NHL, 62 HL cases, and 504 controls. After adjusting for confounding factors, all examined childhood diseases were negatively associated with HL. Measles was negatively associated with NHL, particularly follicular B-cell NHL. Our findings provide additional support to the hypothesis that infections by most common childhood pathogens may protect against HL or, at least, be correlated with some other early exposure, which may lower the risk of HL in adulthood. In addition, our study shows that measles may provide a protective effect against NHL.

Adolescent↗

Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is a well-known complication of chronic lymphocytic leukemia (CLL). In recent years the anti-CD20 monoclonal antibody rituximab has been used for the therapy of steroid-refractory AIHA and autoimmune thrombocytopenia, either idiopathic or in association with CLL. We report the results of rituximab treatment for 14 patients suffering from CLL-associated AIHA. They developed a direct antiglobulin test positive AIHA at a mean time of 47 months (range 0-135 months) from the diagnosis of CLL. In 3 cases AIHA was diagnosed at the same time as CLL. Only 1 patient had fludarabine-related AIHA. All patients received steroids as first-line treatment. At a mean time of 46 days (range 1-210 days) from the diagnosis of AIHA all patients received rituximab at a dosage of 375 mg/m(2)/weekly for 4 weeks. All patients except 3 (2 died of cardiac failure or sepsis soon after the third cycle and 1 HCV-positive patient experienced a rise in serum amino transferases) completed the scheduled four programmed cycles. First injection side effects of rituximab were minimal. All but 2 patients showed an increase in hemoglobin levels in response to rituximab (mean value 3.6 g/dl; range 0.7-10 g/dl) and a reduction in the absolute lymphocyte count and lymph nodes and spleen volume. Nine patients required packed red cell transfusions before starting rituximab; 5 no longer needed transfusions just after the second cycle and another patient after the fourth cycle. Three patients (22%) were considered to fully respond and 7 (50%) only responded partially. At a mean follow-up of 17 months, 8 patients were still alive, 6 of them transfusion-free. Our results prove that the anti-CD20 monoclonal antibody is an effective and well-tolerated alternative treatment for CLL-associated AIHA.

Aged↗

Twenty-four hour ambulatory blood pressure monitoring to evaluate effects on blood pressure of physical activity in hypertensive patients.

OBJECTIVE: Elevated blood pressure is an important risk factor for cardiovascular disease and stroke. Several studies have demonstrated that physical exercise reduces blood pressure levels in hypertensive subjects and improves control of several well-known risk factors for atherosclerosis such as diabetes mellitus, blood lipid profile and obesity. Our group attempted to evaluate if an exercise program based on periodic controlled fast walking sessions would reduce blood pressure levels in hypertensive subjects. DESIGN: We enrolled hypertensive subjects not suffering from obesity (Body Mass Index < 30) already under pharmacological therapy; in these subjects we performed a six-week program of mobility exercise based on fast walking. SETTING: Secondary care. PATIENTS: We enrolled 189 subjects; 168 subjects completed the training period. Entry criteria were Stage I WHO hypertension in pharmacological treatment, BMI < 30, and absence of any pathological condition resulting in reduced mobility. INTERVENTIONS: A six-week mobility program centered on fast walking. MAIN OUTCOME MEASUREMENTS: Systolic and diastolic blood pressure levels before and after the walking program. RESULTS: Mean 24 h systolic blood pressure changed from 143.1 to 135.5 mmHg. Mean 24 h diastolic blood pressure changed from 91.1 to 84.8 mmHg. CONCLUSIONS: This reduction, evaluated with Ambulatory Blood Pressure Monitoring (ABPM), confirms that physical exercise should be a part of lifestyle changes for the management of hypertension both in untreated hypertensive patients or high-risk subjects for hypertension, and also for hypertensive patients in association with pharmacological therapy.

Adult↗

Determining optimum management of descending necrotizing mediastinitis with CT; experience with 32 cases.

To determine the value of helical computed tomography (CT) in the diagnosis, management and outcome of patients suspected of having descending necrotizing mediastinitis (DNM). Thirty-two patients with suspected DNM were submitted to contrast-enhanced single detector-row helical CT, four detector-row CT and 16 detector-row CT of the neck and chest. In 10/32 patients (group 1) no abnormality was observed in the neck or in the chest spaces on CT scan. These patients were all treated non-operatively. In 12/32 patients (group 2) CT showed the presence in the neck spaces of fluid collections, fasciitis, cellulitis, myositis, jugular vein thrombosis and lymphadenopathy; in all these patients the chest was unaffected. A cervical drainage was performed in ten patients. In the remaining ten patients (group 3), the neck infection involved the mediastinal spaces in all the cases and the pleural and pericardial spaces; CT findings included mediastinal cellulitis and fluid collections, pleural and pericardial effusions, venous thrombosis and lymphadenopathy. In these patients, a cervico-mediastinal drainage was performed and antibiotics were administered. The CT provides a highly accurate depiction of the presence and the spread of DNM. The CT findings and the extension of disease are important factors in order to predict for patient management and outcome.

Adult↗

Using multidetector row computed tomography to diagnose and stage pancreatic carcinoma: the problems and the possibilities.

The sensitivity of computed tomography (CT) in the diagnosis of pancreatic neoplasms and accurate tumor staging has significantly been improved by the use of thin-section multi-detector row CT techniques. Greater table speed, improved tube cooling, high resolution imaging and the possibility of isotropic voxels have led to optimal multiplanar reconstruction in any arbitrary plane and particularly along the pancreatic duct and peripancreatic vessels, significantly improving the detection of small pancreatic tumors and surgical resectability where imaging modalities have so far yielded disappointing results. Nonetheless, while multi-detector row CT has greatly enhanced the imaging capabilities of CT, early diagnosis is practically impossible to achieve, since the tumor remains asymptomatic until the surrounding structures are involved. Furthermore, even when treated with radical surgery, the incidence of recurrence is high and the prognosis of pancreatic carcinoma still remains extremely poor and has not changed over the past years. In this article, the recent technical developments of multi-detector row CT in diagnosing pancreatic neoplasms and staging are considered, with special emphasis on multi-detector row CT angiography techniques and curved planar reformations. Some remaining challenging problems such as the pre-operative identification and characterization of small hepatic lesions and detection of omental and peritoneal metastasis, the diagnosis of small isoattenuating pancreatic adenocarcinomas and promising strategies to differentiate between pancreatic adenocarcinoma and chronic inflammatory changes are also presented.

Adenocarcinoma↗

The role of interleukin-3 in classical Hodgkin's disease.

Classical Hodgkin's disease (HD) is a peculiar form of lymphoma characterized by a low frequency of tumor cells, the so-called Hodgkin (H) and Reed/Sternberg (RS) cells, embedded in a background of non-neoplastic (reactive) cells believed to be recruited and activated by H-RS cell-derived cytokines/chemokines. How these tumor cells can survive in such a seemingly hostile environment has confused researchers. We have previously identified interleukin (IL)-3 receptor (R) expression as a common feature of classical HD and unveiled the potential role of IL-3 as a growth and anti-apoptotic factor for H-RS cells. More then 90% of malignant cells of classical HD usually express the alpha chain of the IL-3R (IL-3R(alpha)), as evidenced by immunostaining of frozen sections and cell suspensions from neoplastic lymph nodes. Consistently, HD-derived cell lines (L428, KMH2, HDLM2 and L1236) express the alpha and beta chains that form IL-3R, both at the mRNA and protein level, with a molecular size of IL-3R(alpha) identical (70 kDa) to that expressed by human myeloid cells. Exogenous IL-3 promotes the growth of cultured H-RS cells, such an effect being potentiated by IL-9 and stem cell factor (SCF) co-stimulation, and is able to partially rescue tumor cells from apoptosis induced by serum deprivation. Finally, cultured H-RS cells are able to increase the production of IL-3 by pre-activated T cells, suggesting an involvement of IL-3/IL-3R interactions in the cellular growth of HD through paracrine mechanisms. This review will outline the biological activity of IL-3 and summarize the evidence indicating IL-3 as a growth and anti-apoptotic factor for H-RS cells in classical HD.

Apoptosis↗

Spontaneous chronic subdural hematomas in young adults with a deficiency in coagulation factor XIII. Report of three cases.

Chronic subdural hematomas (SDHs) generally occur in elderly patients. Its pathogenesis is usually related to head trauma with tearing and rupture of the bridging veins, although in some cases a history of trauma is not recognizable. There are many reports regarding the association between spontaneous chronic SDHs and an alteration in coagulative parameters. A coagulative disorder should be suspected when an unexplained hemorrhage occurs, especially in a young patient. The authors report on three young men with a deficiency in coagulation factor XIII (FXIII) who underwent surgery for chronic SDHs. The role of FXIII in the pathogenesis of chronic SDH is emphasized. In patients with unexplained chronic SDH all coagulation parameters and factors should be screened to identify an eventual coagulative disorder.

Adult↗

Pentostatin (2'-deoxycoformycin) for the treatment of hepatosplenic gammadelta T-cell lymphomas.

We report the results of treatment with single agent 2'-deoxycoformycin (Pentostatin) in two patients with Hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), a rare lymphoma subtype with a highly unfavorable prognosis. Present and previous data reviewed here demonstrates the striking cytotoxic activity of Pentostatin against gammadelta+ tumor T cells. Further studies are warranted to define the optimal strategy to fully exploit therapeutic potential of this drug in patients with HSgammadeltaTCL.

Antineoplastic Agents↗

Role of Spiral and Multislice Computed Tomography in the evaluation of traumatic and spontaneous oesophageal perforation. Our experience.

PURPOSE: To assess the role CT in the evaluation of traumatic and spontaneous oesophageal perforation. MATERIALS AND METHODS: From March 2001 to May 2003, we studied 12 patients (7 males and 5 females; age range: 25-66 years, mean age: 43.5 years) with suspected oesophageal perforation due to motor-vehicle accidents (4 cases), stab wound (one case), post-intubation (2 cases), foreign body ingestion (2 cases) and spontaneous (3 cases). Five patients underwent standard chest and cervical radiography; two patients with suspected foreign body ingestion also underwent a gastrografin swallow study; all of the 12 patients underwent CT of the neck, chest and abdomen before and after intravenous, and in four cases oral, administration of contrast material. RESULTS: In 5 patients with cervical, thoracic and abdominal trauma, the CT examination showed the presence of pleuroparenchymal injury (pneumothorax, pleural effusion and subcutaneous emphysema) as well as findings suggestive of oesophageal perforation: peri-oesophageal air (5 cases), peri-oesophageal fluid (4 cases), oesophageal wall thickening (3 cases), oesophageal wall laceration (2 cases) with abnormal course of the nasogastric tube in one of them and extraluminal extravasation of oral contrast material (2 cases). In 2 patients with post-intubation complications, CT showed the presence of a small peri-oesophageal fluid collection containing small gas bubbles in one case, and a gross perioesophageal abscess-like collection in the second case. In the 2 patients with foreign body ingestion, the plain radiography associated with CT showed the presence of a thin metal object in the cervical region (fragment of a dental plate) and a small extraluminal extravasation of gastrografin in one case, whereas in the other case CT showed the presence of a foreign body (chicken bone) in the hypopharynx with oesophageal wall thickening and peri-oesophageal oedema. In the remaining three patients with suspected spontaneous oesophageal perforation, CT showed the presence of a intramural haematoma in one case, oesophageal fluid distension with gas and a small peri-oesophageal fluid effusion (Mallory-Weiss syndrome) in another, and oesophageal rupture (Boerhaave syndrome) in the last case. CONCLUSIONS: Our experience shows that in patients with suspected traumatic and spontaneous oesophageal perforation, standard cervical and chest radiography may suggest a suspected oesophageal perforation in only a small proportion of cases, whereas oral contrast oesophagography has a higher sensitivity. Through the careful analysis of suggestive and specific signs of oesophageal perforation, a correct CT examination enables an accurate and timely diagnosis which significantly affects prognosis and provides valuable indications for treatment.

Accidents, Traffic↗

Non-Hodgkin's lymphoma and hepatitis C virus: a case-control study from northern and southern Italy.

HCV has been associated with NHL, but the evidence from case series and case-control studies is not totally consistent. Between 1999 and 2002, we conducted a hospital case-control study on the association between HCV, HBV and NHL in 2 areas of Italy where HCV infection is relatively frequent. Cases (n = 225, median age 59 years) were consecutive patients with a new diagnosis of NHL admitted to local specialized and general hospitals. Controls (n = 504, median age 63 years) were patients with a wide spectrum of acute conditions admitted to the same hospitals as cases. HCV prevalence was 19.6% among NHL cases and 8.9% among controls (adjusted OR = 2.6, 95% CI 1.6-4.3). The ORs for HCV were similar for low-grade and intermediate-/high-grade B-cell NHL (3.2 and 2.4, respectively) as well as for nodal and extranodal NHL (2.7 and 2.6, respectively). Positivity for HBsAg was found in 3.8% of cases and 0.9% of controls (OR = 4.1, 95% CI 1.2-14.4). An elevated OR was also found for history of hepatitis C (OR = 4.7, 95% CI 2.3-9.5). History of blood transfusion before 1990 was associated with HCV positivity among controls but not with NHL risk. In conclusion, HCV infection was associated with an increase in NHL risk, and the fraction of NHL cases attributable to HCV was 12.4% (range 6.3-18.5%).

Adolescent↗

CD26 expression correlates with a reduced sensitivity to 2'-deoxycoformycin-induced growth inhibition and apoptosis in T-cell leukemia/lymphomas.

PURPOSE AND EXPERIMENTAL DESIGN: dCF (2'-deoxycoformycin) is a potent inhibitor of ADA (adenosine deaminase), an enzyme regulating intra- and extracellular concentrations of purine metabolites. ADA exists as cytosolic and extracellular forms, the latter colocalized on the cell surface with CD26. Once the surface expression of CD26 and ADA in a panel of cell lines and primary samples of T-cell leukemia/lymphoma was defined, we correlated this expression with the antiproliferative and apoptotic effect of dCF. RESULTS: Surface expression of CD26 inversely correlated with the capability of dCF to inhibit cell growth and induce apoptosis both in T-cell lines and primary samples of T-cell malignancies. This conclusion was sustained by a decreased sensitivity to dCF-mediated proapoptotic and/or antiproliferative in vitro effects of: (a) leukemia/lymphoma T-cell lines expressing surface CD26/ADA complex; (b) primary CD26(+) T cell malignancies; and (c) normal T cells (CD26(+)) as compared with tumor T cells (CD26(-)) in unpurified samples from three cases of T-cell receptor gammadelta(+) T-cell malignancies characterized by a mixture of normal and neoplastic cells. This latter point was confirmed in vivo, in a patient affected by CD26(-) T-cell receptor gammadelta(+) hepatosplenic gammadelta(+) T-cell lymphomas treated on a compassionate basis with dCF. The inverse correlation between CD26 expression and sensitivity to dCF was also demonstrated in a lymphoblastic lymphoma case in which CD26 was expressed on circulating blasts at relapse but not at diagnosis, as well as in two H9 T-cell clones expressing or not expressing CD26 mRNA and protein. CONCLUSIONS: This study corroborates the notion of CD26 as a marker of poor prognosis for T-cell malignancies and delineates a role for CD26 as a predictor of poor response to dCF.

Antibiotics, Antineoplastic↗