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Biomedical subjects

F Perfetto

Publications and source records attributed to F Perfetto.

At least 37 records · Page 2Linked to original sources

Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia.

The t(12;21)(p13;q22) translocation has been described recently as the most recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It has also been associated with B-precursor lineage involvement and good outcome. We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we report three cases with hybrid phenotype, and two cases showing an aggressive and fatal disease. Our data show that the t(12;21) does not represent an independent good-risk indicator. Long follow-ups and additional molecular investigations are needed to assess the prognostic and pathogenetic relevance of t(12;21) in childhood ALLs.

Cell Lineage↗

Persistence of E2A/PBX1 transcripts in t(1;19) childhood acute lymphoblastic leukemia: correlation with chemotherapy intensity and clinical outcome.

The occurrence of t(1;19) translocation was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) for the E2A/PBX1 hybrid message in a panel of 37 consecutive childhood acute lymphoblastic leukemias (ALLs). Three patients with B-precursor ALL were found to be positive at diagnosis and were re-tested during follow-up to assess the presence of minimal residual disease (MRD). Two of them became PCR-negative during treatment, whereas one remains positive 3 years after diagnosis. Since all three patients are presently in clinical and hematological complete remission, PCR detection of persistent E2A/ PBX1 transcript does not seem to affect significantly the DFS at 3 years. However, the predictivity for an eventual late relapse still remains to be assessed.

Adolescent↗

[The reduction of ferromagnetic artifacts by using a fast-spin-echo sequence in the postoperative assessment of degenerative diseases of the cervical spine].

This study was aimed at investigating if fast spin echo (FSE) pulse sequences can increase the diagnostic capabilities of MRI in the patients with degenerative disease of the postoperative cervical spine, considering their lower magnetic susceptibility than that of conventional spin echo (SE) sequences. The patient population consisted of 15 patients submitted to diskectomy after Cloward and Caspar. MR images were acquired with a 1.5-T unit (Signa, General Electric) with T2-weighted FSE versus conventional T1- and T2-weighted SE images. Thanks to fewer metallic artifacts, FSE images of the postoperative cervical spine yielded more pieces of information than conventional SE sequences in demonstrating the spine and its content. The best results were obtained in the patients with canal stenosis (8 patients) and myelomalacia (2 patients). In addition, the myelographic effect, another major semiologic feature of the FSE technique, provided further diagnostic information in these patients. Moreover, shorter examination times resulted in better patients tolerance, especially in those with recent surgery. Finally, reducing motion, blood flow or CSF flow artifacts definitely improved FSE image quality.

Aged↗

[Magnetic resonance myelography with a fast-spin-echo sequence].

A major application of Magnetic Resonance Imaging (MRI) consists in the "myelographic effect", characterized by high signal intensity of the CSF, which permits to visualize spinal subarachnoid spaces and nerve root sheaths. Such new ultrafast pulse sequences as fast spin echo (FSE) further enhance CSF high signal intensity. In addition, suppressing background with the fat suppression technique and with maximum intensity projection (MIP), a particular algorithm already used in MR angiography, FSE sequences yield 3D myelography-like images. Our study was aimed at assessing the clinical role and the reliability of this technique. Our preliminary experience is based on 21 patients with pain in the lower back and legs and on 5 healthy volunteers; all the myelography-like images were obtained with a 1.5-T MR system (Signa, General Electric). The parameters for FSE myelography-like images included: TR = 6000, TE = 200, ETL = 32, thickness = 3 mm, matrix = 256 x 224, Nex = 4, FOV = 20 cm, fat presaturation, no phase wrap, acquisition time = 2 min 58 s. MR myelography sequences were acquired after a standard FSE T1/T2-weighted exam. MR-myelography results confirmed the diagnosis of disk herniation made on conventional T1/T2-weighted images, especially in thecal sac compression and/or amputation of nerve root sheaths. MR myelography appeared to be especially useful in migrated disk herniation or in abnormal origin of nerve roots. Moreover, it allowed full and panoramic visualization of the subarachnoid spaces and excellent definition of the thecal sac, nerve roots and nerve root sheaths. In one patient only movement artifacts affected image quality. To conclude, even though it fails to yield any functional information, MR myelography appears to be an easy, rapid and noninvasive support to conventional MRI of the lumbar spine, to replace conventional myelography.

Female↗

[Imaging with magnetic resonance imaging of the operated cervical spine].

The Authors report their personal experience with postoperative neuroradiologic studies in surgical patients with a herniated disk and/or degenerative cervical spondylosis. Twenty-six patients were enrolled: 16 of them underwent anterior diskectomy, 7 posterior decompressive laminectomy and 3 vertebral body removal. The patients were submitted to pre- and postoperative MRI with high field equipment (Signa 1.5 T, General Electrics), using sagittal SE T1- (TR/TE 360/15), PD and T2-weighted (TR/TE/FA 2000/40/120) sequences and T2-weighted GE axial sequences (TR/TE/FA 400/34/30). FSE sequences (TR/TE/ETL 4000/95/8) were used in 15 cases instead of the above T2-weighted SE sequences. The main postoperative MR findings were analyzed. In particular, the morphological and signal features of bone grafts, of vertebral end-plates, of the subchondral bone and of the surgical site were studied. After anterior diskectomy, the most frequent MR features were massive signal changes in the bone graft and lower vertebral plates, which were hypointense in T1 and hyperintense in T2; the adjacent subchondral bone also exhibited signal changes. Other postoperative MR findings accounted for early postoperative mobility (4 cases of persistent myelomalacia and 3 of bone graft fracture with consequent spinal instability) and late mobility (2 cases of herniated disk, 5 of spinal stenosis and one pseudomeningocele). The main limitation of MRI in postoperative cervical spine studies was the presence of ferromagnetic artifacts during SE, and even more GE, sequences; these artifacts were the main cause of misdiagnoses. In our experience, this troublesome limitation was overcome with FSE sequences but diagnostic accuracy remained poor in 4 patients. MRI, thanks to its multiparametric and multiplanar yield, is the gold standard for the examination of several early and late postoperative features and of postoperative mobility in the cervical spine. Moreover, T2-weighted FSE acquisitions are better than conventional SE to this purpose, because examination time is shorter, myelographic effect is improved and the sensitivity to ferromagnetic artifacts reduced.

Adult↗

Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients.

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02 +/- 2.9 pg/ml vs 4.4 +/- 1.1 pg/ml and 3.08 +/- 0.7 pg/ml, respectively; P < 0.001). No difference was demonstrated between diabetic patients without angiopathy and controls. These findings suggest that ET-1 may be a marker for arterial vascular disease only in patients with overt angiopathy. It is unclear whether it participates in the endothelial injury process or it is merely released from damaged endothelial cells.

Biomarkers↗

Daytime circulating melatonin levels in smokers.

AIMS AND BACKGROUND: Melatonin secretion is required to be a potential inhibitor of the development and growth of tumors, and cigarette smoking is a well established risk factor for cancer at various sites. METHODS: Circulating melatonin levels of 20 smokers and 20 non smokers (controls), sampled at the same hour from awaking in order to obtain a comparable circadian synchronization, were compared. RESULTS: Our data showed higher melatonin circulating levels in smokers (17.44 +/- 1.8 pg/ml) than in nonsmokers (9.77 +/- 1.4 pg/ml). CONCLUSIONS: The causes, mechanism and meaning of this phenomenon are still unknown. The most attractive hypothesis considers higher melatonin levels in smokers as an attempt to counterbalance cellular growth stimulus, a natural "brake" mechanism to restrain the proliferation of normally differentiated tissues: smoke is a prominent risk factor for several different tumors.

Adult↗

Comparison between venoconstrictor effects of sumatriptan and ergotamine in migraine patients.

The vasoconstrictor activity of sumatriptan and ergotamine were compared by injecting these drugs in the hand vein of migraine subjects. We used the "venotest method", which permits the evaluation of the venoconstrictor effect of small doses of drugs, acting locally in the hand vein. Sumatriptan injected at increasing doses in the hand vein provoked contraction only at high doses (500 micrograms): venoconstriction lasted 5-15 minutes and was similar in intensity and duration to that induced by 0.5-1 micrograms of 5-hydroxytryptamine (5-HT). Likewise, ergotamine induced contraction only at a dose of 50 micrograms: this venoconstrictor effect was long lasting (at least 1 hour). Ergotamine-induced hand vein contraction, almost completely inhibited by ketanserin, seems mediated at least in part by 5-HT2 receptors, like the one induced by 5-HT and sumatriptan, already observed in a previous study. Clinical doses of ergotamine (0.25 mg intramuscular) and of sumatriptan (6 mg subcutaneous) do not provoke hand vein contraction for at least 1 hour: this could be due to a low activity of these drugs on the 5-HT2 vein receptors or a technique that is unsuitable to detect the vasoconstrictor effect of drugs given by the systemic route. The long lasting venoconstrictor effect of ergotamine may be due to a slow dissociation from receptor sites. The short vasoconstriction induced by sumatriptan could account for the recurrence of headache in many sumatriptan-treated migraine subjects.

Adult↗

Chronobiology in epidemiology and preventive medicine.

Many of the known cardiovascular risk factors, such as hormones, metabolic parameters, lifestyle, blood pressure, fibrinogenesis, fibrinolytic activity, etc., and also the reactivity of the organism to stimuli, are periodical and therefore require adequate measures at specific times in appropriate frequencies. The presence of circadian, circannual or other wide frequency rhythms may lead to contradiction in the evaluation of a potential risk factor. Chronobiological analysis shows fine differences within a "risk variable", defining some characters which may imply the alteration of a parameter only at certain times. Periodical risk factors may therefore be foreseen and sometimes prevented. Moreover, chronobiological approach may show another peculiar relation between risk factors; this is the so-called chronorisk. The convergence, in certain periods of time, of the phases of various risk factors, may strengthen their combined value. On the other hand, the phases of the protective factors, in the same period of time, may contribute to reduce or strengthen this combined value. From this point of view combined risk, apparently unimportant, appears highly increased, as compared with the normal homeostatic value. At equal levels of risk factors, different distribution and amplitude of the phases implies great differences in final combined risk values. Acute heart attack has a daily, seasonal and perhaps ultradian rhythm; other cardiological events, such as angina pectoris and sudden death, have circadian rhythms. Also cerebral vascular events have daily, seasonal, weekly and monthly variations. The periodical variations of acute vascular events and of the related risk factors, near and far, implies many complex interrelations in timing of biological structures, which are still perceived by the physician only as "noise".

Chronobiology Phenomena↗

[The enzymatic mechanisms involved in the pathogenesis of rheumatoid arthritis and arthrosis. The role of metalloproteases and serine proteases in the breakdown of articular cartilage].

Rheumatoid arthritis and osteoarthritis, expression, respectively, of inflammatory and degenerative articular involvement, are the most important diseases affecting joint cartilage. Proteolytic enzymes are the effectors of the articular damage: their increased production by chondrocytes and synoviocytes leads to cartilage breakdown. These enzymes, whose structure and specific activities have been defined in the recent years, carry out their action in the extracellular matrix. They are characterized by the presence of a particular element at the active site, that allows to distinguish four different families. The most studied and the best known among them are metalloproteinases, represented by several enzymes with common features, and serinoproteinases, some members of which, particularly urokinase and tissue-type plasminogen activator, are recently indicated as potential responsible for articular destruction. Activators, and inhibitors of proteinases play a fundamental role: a fine balance, that controls the mechanisms of activation and inhibition, seems to take place at transcriptional level. Any factor able to modify the cellular shape and the cytoskeleton, gives rise to lytic enzyme expression at the genomic level. With the progress of knowledges, serinoproteinases are assuming an increasing relevance, particularly the components of the fibrinolytic pathway.

Arthritis, Rheumatoid↗

Evidence for bone mass and body fat distribution relationship in postmenopausal obese women.

The measurement of bone mass, a reliable predictor of osteoporotic fractures, in obese subjects has yielded conflicting results and bone mass has been reported to be elevated, normal or decreased. These observations indicate that factors other than body weight may be involved in the less risk for osteoporosis in obese subjects. In order to clarify the role of body fat distribution on bone density we studied sixty postmenopausal overweight/obese women with Body Mass Index (BMI) over 25 kg/m(2). Thirty five age-matched, nonobese postmenopausal women, served as controls. Bone mineral density (BMD) was measured at the proximal and ultradistal non dominant forearm using a double energy X-ray absorption (DEXA) apparatus. The waist/hip circumferences ratio (WHR) was used, in obese group, as an anthropometric estimation of the abdominal (WHR>0.85) to lower-extremity (WHR>0.85) fat proportion. The results were analyzed by Student t-test, ANOVA, and multiple linear regression analysis. No difference was found in BMD between obese group and controls, but a highly significant (P<0.001) positive correlation has been documented between proximal and ultradistal radius bone mineral density and waist/hip ratio in the obese group. Instead not significant correlation was found with BMI. Regional fat topography may influence the bone mass independently of total adiposity and visceral fat was the primary parameter accounting for higher bone mineral density values. These finding suggest that women with android-like obesity are protected from osteoporosis.

Journal Article↗

Influence of non-insulin-dependent diabetes mellitus on plasma endothelin-1 levels in patients with advanced atherosclerosis.

Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen properties. Increased circulating ET-1 levels were found in patients with atherosclerosis as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The aim of the present study was to ascertain the influence of the NIDDM on plasma ET-1 levels in patients with advanced atherosclerotic lesions. The circulating ET-1 levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis without NIDDM. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8 pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant relationship was found between age and ET-1 concentrations, and no differences were noted between men and women in the control group. This study demonstrated that circulating ET-1 levels are increased in patients with atherosclerosis and that those with NIDDM showed the highest ET-1 levels. These observations strongly support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest that this peptide may be involved in the development of atherosclerotic lesions in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and hypertriglyceridemia in the diabetic patients could account for the increased ET-1 levels found in these patients.

Adult↗

Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study.

The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.

Adult↗