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Biomedical subjects

A Ferrari

Publications and source records attributed to A Ferrari.

At least 55 records · Page 3Linked to original sources

Emerging problems in the pharmacology of migraine: interactions between triptans and drugs for prophylaxis.

Patients suffering from migraine take drugs for many years in order either to relieve or to prevent recurrent migraine attacks. When two or more drugs are co-administered, there is always the possibility of drug-drug interaction. Interactions can be either kinetic or dynamic. The former are the most frequent ones. Mechanisms of kinetic interaction can be different, but the most common are represented by the induction or inhibition of enzymes of the cytochromes p450 (CYP) system. This system plays an important role in the disposition of a large number of drugs, including those used for migraine. This review examines the interactions between triptans-the most effective drugs for the therapy of migraine attacks-and drugs for migraine prophylactic treatment.

Analgesics↗

Advanced ovarian carcinoma: usefulness of [(18)F]FDG-PET in combination with CT for lesion detection after primary treatment.

AIM: To determine the additional value of [(18)F]FDG-PET in combination with computed tomography (CT) over CT used alone, for evaluating ovarian cancer patients after primary treatment. METHODS: Twenty-five women (mean age: 53.6 years) had primary debulking surgery followed by chemotherapy for histologically proven ovarian carcinoma. At initial diagnosis, the tumor types were papillary serous adenocarcinoma (n=20), endometroid carcinoma (n=3), mixed mullerian tumor (n=1), and granulosa cell tumor (n=1). All patients underwent [(18)F]FDG-PET and contrast enhanced CT examinations, within 30 days of the completion of chemotherapic treatment. [(18)F]FDG-PET images were interpreted with the knowledge of CT findings (PET+CT); conversely, CT images were evaluated with no knowledge of the [(18)F]FDG-PET results. Within 7 day of imaging studies, 2(nd)-look laparoscopy (n=7) or laparotomy (n=18) was performed for histological confirmation. In all cases, imaging findings were then correlated with results of histopathologic examination. RESULTS: Of the 23 neoplastic viable lesions, all histologically confirmed, 16 could be detected by CT alone and 19 by PET+CT. An inflammatory lymph-node was misdiagnosed as viable tumor with both PET+CT and CT alone; an area of scar tissue in the presacral region was also misinterpreted as malignant tissue with CT alone. Overall lesion-based sensitivity, specificity and accuracy in assessing focal areas of residual tumor were as follows: 69.56%, 83.33%, 74.28% for CT, and 82.60%, 91.67%, 85.71% for PET+CT. The negative predictive value of PET+CT was markedly higher (73.33%), compared to that of CT alone (58.82%). CONCLUSION: PET used in combination with CT allows to accurately assess tumor response. A major advantage of PET+CT over CT alone is in excluding the presence of residual viable lesions after treatment.

Adult↗

Emergency laparoscopic splenectomy for "wandering" (pelvic) spleen: case report and review of the literature on laparoscopic approach to splenic diseases.

Wandering spleen (WS) is a rare condition where the spleen, free from its ligaments, is allowed to move inside the abdomen predisposing the patient to life-threatening complications due to torsion of the vascular pedicle; splenic infarction, portal hypertension, bleeding and acute abdomen may occur. WS is rarely suspected at presentation since symptoms are usually not specific and definitive diagnosis is usually reached only by imaging technologies such as color flow ultrasonography and angio-spiral computer tomography. A 42-year-old woman was referred to our institute from the Emergency and Accident ward, complaining of a sudden onset of sharp abdominal pain together with nausea and vomiting. At examination a large, painful mass was present on the left middle-lower abdominal quadrant. A pelvic spleen was revealed at abdominal ultrasonography (US) and confirmed by abdominal CT. Emergency laparoscopy was carried out. The spleen was barely attached to the peritoneum of the anterior abdominal wall, covered by the greater omentum, the small bowel, and the transverse colon. Once mobilization of the spleen was concluded, the vascular pedicle appeared torted and thrombosed and laparoscopic splenectomy was performed. The patient was discharged on the 4th postoperative day with no complications. To date, only 5 cases of laparoscopic approach to WS have been reported. A review of the literature confirms that the reduction of postoperative stay, wound complications, and overall morbidity and a faster return to normal activity make laparoscopy the "gold standard" approach to the spleen as for treatment of many hematological disorders or more unusual splenic diseases.

Abdominal Pain↗

Thrombotic thrombocytopenic purpura and pregnancy: a case report and a review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.

Adult↗

Paratesticular rhabdomyosarcoma: report from the Italian and German Cooperative Group.

PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years. PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients. RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor. CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent-free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse.

Adolescent↗

Immunohistochemical study of muscle biopsy in children with cerebral palsy.

Muscle biopsy was examined in 20 children with cerebral palsy, using immunohistochemical methods for marker of denervation neural cell adhesion molecules (N-CAM) in addition to standard techniques. Histological and histochemical study showed mild myopathic changes, type 1 predominance, and type 1 and type 2 hypotrophy, in accord with previous observations. Immunohistochemical study showed N-CAM expression in most biopsies (15/20), usually in scattered fibers, whereas in four patients aged less than 6 years it was expressed in grouped fibers. Our study supports the hypothesis of motor unit remodeling as a consequence of spasticity, especially in early phases of the disease.

Adolescent↗

Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis.

BACKGROUND: Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM: To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS: Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS: Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS: In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.

Aged↗

Dermoscopic diagnosis by a trained clinician vs. a clinician with minimal dermoscopy training vs. computer-aided diagnosis of 341 pigmented skin lesions: a comparative study.

BACKGROUND: In the last few years digital dermoscopy has been introduced as an additional tool to improve the clinical diagnosis of pigmented skin lesions. OBJECTIVE: To evaluate the validity of digital dermoscopy by comparing the diagnoses of a dermatologist experienced in dermoscopy (5 years of experience) with those of a clinician with minimal training in this field, and then comparing these results with those obtained using computer-aided diagnoses. METHODS: Three hundred and forty-one pigmented melanocytic and non-melanocytic skin lesions were included. All lesions were surgically excised and histopathologically examined. Digital dermoscopic images of all lesions were framed and analysed using software based on a trained artificial neural network. Cohen's kappa statistic was calculated to assess the validity with regard to the correct diagnoses of melanoma and non-melanoma. RESULTS: Sensitivity was high for the experienced dermatologist and the computer (92%) and lower for the inexperienced clinician (69%). Specificity of the diagnosis by the experienced dermatologist was higher (99%) than that of the inexperienced clinician (94%) and the computer assessment (74%). Notably, computer analysis gave a higher number of false positives (26%) compared with the experienced dermatologist (0.6%) and the inexperienced clinician (5.5%). CONCLUSIONS: Our results indicate that analysis either by a trained dermatologist or an artificial neural network-trained computer can improve the diagnostic accuracy of melanoma compared with that of an inexperienced clinician and that the computer diagnosis might represent a useful tool for the screening of melanoma, particularly at centres not experienced in dermoscopy.

Adolescent↗

Study of the dosimetric characteristics of cosmic radiation at civil aviation altitudes.

The dependence of the doses on solar activity for intermediate levels of the solar modulation parameter has been studied by means of simulations carried out by the Monte Carlo transport code FLUKA. The vertical cut-off rigidities investigated lie between 0.4 and 6.1 GV. The calculated results show that the linear dependence proposed in a previous work, for the effective dose rate as a function of the solar modulation parameter, can be considered as an acceptable approximation. In addition, some dosimetric characteristics of cosmic radiation and some properties of the dosemeters in use for monitoring in the cosmic ray environment have been analysed with a view to simplifying measurements. The depth-dose curves in the ICRU sphere and the response of a tissue-equivalent ionisation chamber have been determined by the FLUKA code for a number of cosmic ray spectra On the basis of the calculated results, it is concluded that a value of the depth. d, which would make the ambient dose equivalent a conservative predictor of the effective dose, cannot be specified for cosmic radiation. However, the operational quantity can be useful in order to verify the predictions of Monte Carlo calculations. It is demonstrated that a crude approximation of the ambient dose equivalent could be obtained by multiplying by 2 the absorbed dose measured by a tissue-equivalent ionisation chamber with wall thickness of 10 mm.

Aircraft↗

Nuclear reactions in Monte Carlo codes.

The physics foundations of hadronic interactions as implemented in most Monte Carlo codes are presented together with a few practical examples. The description of the relevant physics is presented schematically split into the major steps in order to stress the different approaches required for the full understanding of nuclear reactions at intermediate and high energies. Due to the complexity of the problem, only a few semi-qualitative arguments are developed in this paper. The description will be necessarily schematic and somewhat incomplete, but hopefully it will be useful for a first introduction into this topic. Examples are shown mostly for the high energy regime, where all mechanisms mentioned in the paper are at work and to which perhaps most of the readers are less accustomed. Examples for lower energies can be found in the references.

Computer Simulation↗

Renal tubular events following passage from the supine to the standing position in patients with compensated liver cirrhosis: loss of tubuloglomerular feedback.

BACKGROUND AND AIMS: Patients with preascitic liver cirrhosis display significant renal sodium retention in the upright posture and an exaggerated natriuresis during recumbency. To date, intrarenal sodium handling in these patients has not been studied using lithium clearance and fractional excretion techniques during recumbency and orthostatism. METHODS: Ten patients with preascitic (Child-Pugh A) liver cirrhosis and 10 healthy subjects underwent the following measurements during recumbency and then after four hours of standing: (a) active renin and aldosterone plasma levels; and (b) renal clearance of creatinine, sodium, potassium, and lithium (an index of fluid delivery to the loop of Henle). RESULTS: Unlike the control group, in the upright posture patients had significantly lower values of lithium clearance and fractional excretion compared with recumbency (21.6 (8.6) v 30.5 (10.2) ml/min (p<0.03) and 12.8 (4.4)% v 20.8 (4.9)% (p<0.01), respectively). Our patients showed maintenance of the glomerular-tubular balance-that is, the correlation between creatinine clearance and proximal tubular reabsorption of fluid-during both recumbency and in the upright posture (r=0.96, p<0.001; r=0.97, p<0.001, respectively). In contrast, patients displayed tubuloglomerular feedback only in the supine position. This was demonstrated by the observation of a negative correlation between lithium fractional excretion (a measure of the fractional delivery of sodium to the distal nephron) and filtered sodium load only in recumbency (r=-0.73; p< 0.03) and not during standing (r=0.22; p> 0.05). CONCLUSIONS: This study suggests that both the reduction in fluid and sodium delivery to the distal nephron and loss of tubuloglomerular feedback (the mechanism increasing glomerular filtration rate when the distal tubule is reached by a reduced sodium load) contribute towards the tendency to sodium retention in compensated cirrhosis during prolonged upright posture.

Adult↗

[Ulcero-necrotic and lymphoproliferative naso-paranasal lesions in cocaine abuse].

In this work are reported two clinical cases of cocaine abusers with destructive lesions of nasal-paranasal cavities. The clinical presentation and the absence of a positive history of drug addiction led to a differential diagnosis between lymphoma, idiopathic median line granuloma and Wegener granulomatosis. Biochemical and serological examinations did not prove conclusive. The diagnosis was finally formulated on the basis of the documented presence of cocaine in the biological fluids. Emphasis is placed in the difficulty of obtaining a reliable case history in this type of patients. Moreover, the Authors point out that it is advisable to test for drugs in the biological fluids prior to undertaking time-consuming diagnostic procedures for pathologies which are extremely rare in the West countries.

Adult↗

Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group.

BACKGROUND: Hemangiopericytoma (HPC) is very uncommon in childhood and comprises two different clinical entities, the adult type and the infantile type, occurring in the first year of age. We report on a series of 27 pediatric patients treated from 1978 to 1999 by the Italian and German Soft Tissue Sarcoma Cooperative Group. METHODS: Seven patients had infantile HPC; complete resection was achieved in the tumors of five patients and chemotherapy was given to four patients. Twenty children had adult type HPC; nine received complete tumor resection (four patients at diagnosis and five at delayed surgery). Post-operative radiotherapy was administered to 15 patients, chemotherapy to 19. RESULTS: Six of seven patients with infantile HPC were alive in first remission; one patient died of disease. Chemotherapy achieved an objective response in four of four patients. Among the adult type HPC cases, 5-year event free survival was 64% (median follow-up 125 months); 12 patients were alive in first remission, eight patients relapsed and died of disease. Seven of 10 evaluable patients showed good response to chemotherapy. Statistically significant differences in outcome were observed in relation to Intergroup Rhabdomyosarcoma Study grouping, size, local invasiveness, and gender. CONCLUSIONS: Infantile HPC is a unique entity probably related to infantile myofibroblastic lesions and characterized by a high response to chemotherapy, which is required in case of unresectable, life-threatening tumors. In children over 1 year of age, HPC behaves like its adult counterpart; complete surgical resection remains the mainstay of treatment, but chemotherapy and radiotherapy seem effective and are recommended in all patients with incomplete tumor resection and/or locally invasive, large tumors.

Adolescent↗

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity.

In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for their cytotoxic activity in vitro against H460 non-small lung carcinoma cell line, the activity being for 24 out of 37 compounds in the 0.01-0.3 microM range. A QSAR analysis indicated that lipophilicity is the main parameter correlated with cytotoxicity. Investigation of the DNA-Topo I-drug cleavable complex showed a rough parallelism between cytotoxicity and inhibition of Topo I. Persistence of the DNA cleavage after NaCl-mediated disruption of the ternary complex suggests that for the most potent compounds, e.g., 15, the cytotoxicity was at least in part related to stabilization of the complex, as also supported by the persistence of the DNA-enzyme complex in drug-treated cells. The in vivo antitumor efficacy of the most potent analogue (15) was evaluated in direct comparison with topotecan using human lung tumor xenograft models. In the range of optimal doses (2-3 mg/kg), the improved efficacy of 15 was documented in terms of inhibition of tumor growth and rate of complete response.

Animals↗

In vivo tracking of bone marrow fibroblasts with fluorescent carbocyanine dye.

Recent advances in the field of tissue engineering have culminated in new tissue substitutes that combine a biomaterial and precursor cells. The effectiveness of these materials is generally assessed in animals, but few studies explore the fate of the transplanted cells in vivo, despite its paramount importance for understanding the function of the engineered tissues. Current methods that use reporter genes or chimeric animals are not always well suited to solving tissue-engineering problems. We therefore developed a new method for irreversible labeling of cells to track their fate in vivo. We used a fluorescent lipophilic probe, CM-Dil, that avidly binds to the cell membrane. Human bone marrow stromal fibroblasts could be labeled with 20 microM CM-Dil in 30 min. The CM-Dil was not cytotoxic and did not affect cell proliferation in vitro. Cells could be monitored for up to 30 days when placed in a coral scaffold and implanted intramuscularly or in a bony site. However, the fluorescence intensity decreased roughly in parallel with the number of cell divisions. This fact needs to be taken into account during the design and interpretation of experiments. We believe that this technique is also of interest for other cell types.

Bone Marrow Cells↗

Low-dose chemotherapy with methotrexate and vinblastine for patients with advanced aggressive fibromatosis.

BACKGROUND: This Phase II study was undertaken to assess the activity of methotrexate plus vinblastine in the treatment of patients with inoperable aggressive fibromatosis (AF) and to observe the evolution of the disease after such low-dose chemotherapy. METHODS: Thirty patients with a median age of 27 years who were affected by primary (20%) or recurrent (80%), advanced, inoperable AF were treated with weekly methotrexate at a dose of 30 mg/m(2) plus vinblastine at a dose of 6 mg/m(2) for a median interval of 1 year. Patients with recurrent disease had received surgery, radiotherapy, tamoxifen, and antracycline-based chemotherapy. Tumor response was assessed in all patients as well as time to disease progression. RESULTS: Eighteen patients (60%) showed stable disease or minor tumor shrinkage along with symptom relief. A partial response was detected in 12 patients (40%). No complete responses were observed, and no patients had tumor progression during treatment. Four patients received fewer than 15 cycles of chemotherapy, mainly because of severe myelotoxicity. One of these patients died of local disease progression 33 months later, and the other three patients were stable. After a median follow-up of 75 months, the 10-year actuarial progression free interval is 67%. CONCLUSIONS: Methotrexate plus vinblastine given every 7-10 days for several months is associated with prolonged stable disease in a substantial subset of patients with advanced (inoperable) aggressive fibromatosis.

Adult↗

Visualization of in vivo direct interaction between HIV-1 TAT and human cyclin T1 in specific subcellular compartments by fluorescence resonance energy transfer.

Human cyclin T1, a component of the P-TEFb kinase complex, was originally identified through its biochemical interaction with the Tat transactivator protein of human immunodeficiency virus type 1 (HIV-1). Current understanding suggests that binding of Tat to P-TEFb is required to promote efficient transcriptional elongation of viral RNAs. However, the dynamics and the subnuclear localization of this process are still largely unexplored in vivo. Here we exploit high resolution fluorescence resonance energy transfer (FRET) to visualize and quantitatively analyze the direct interaction between Tat and cyclin T1 inside the cells. We observed that cyclin T1 resides in specific subnuclear foci which are in close contact with nuclear speckles and that Tat determines its redistribution outside of these compartments. Consistent with this observation, strong FRET was observed between the two proteins both in the cytoplasm and in regions of the nucleus outside of cyclin T1 foci and overlapping with Tat localization. These results are consistent with a model by which Tat recruits cyclin T1 outside of the nuclear compartments where the protein resides to promote transcriptional activation.

Animals↗

Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin.

A series of new 7-iminomethyl derivatives of camptothecin were obtained from camptothecin-7-aldehyde and aromatic, alicyclic and aliphatic amines. Their hydrogenation led to the corresponding amines. All the imines and the less polar amines showed a marked increase of the cytotoxic activity against H460 non-small lung carcinoma cell line, with respect to topotecan. The lipophilicity of the substituent in position 7 of camptothecin seems to play an important role for cytotoxic potency. The 7-phenyliminomethyl derivative showed efficacy comparable to topotecan in vivo against NSCLC H460 xenografted in athymic nude mice.

Animals↗