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G Mariani

Publications and source records attributed to G Mariani.

At least 73 records · Page 4Linked to original sources

Successful treatment of hepatosplenic candidiasis in an elderly patient with acute myeloid leukemia using liposomal daunorubicin and fluconazole.

Fungal infections are an increasing cause of morbidity and mortality in patients with haematological malignancies. The organism most often responsible are Candida spp., particurarly Candida Albicans. This report describes our experience in a 63-year-old man who developed symptoms of hepatosplenic candidiasis caused by Candida tropicalis after treatment for acute myeloid leukaemia (AML). The fungal infection was successfully controlled using fluconazole, and the patient has been disease-free for more than 11 months after antileukemic chemotherapy without any recurrence of Candida infections. Our experience suggests that AML and chemotherapy associated fungal infections can be controlled with an appropriate therapeutic regimen.

Antibiotics, Antineoplastic↗

Immune tolerance in hemophilia with factor VIII inhibitors: predictors of success.

BACKGROUND AND OBJECTIVES: Long term administration of high doses of factor VIII (FVIII) was shown to eliminate alloantibodies to FVIII (FVIII inhibitors). This procedure is widely referred to as immune tolerance (IT). DESIGN AND METHODS: In 1989 an international registry of IT protocols was created which recruited 314 patients with severe hemophilia A (HA) and an inhibitor who were given IT treatment. RESULTS: Fifty hemophilia care centers worldwide contributed data to the registry; 94.8% of the patients were high responders. The median inhibitor titer prior to IT (pre-titer) was 7 BU (range 0-720). The FVIII doses ranged from <50 International Units (I.U.)/kg/b.w./day to >200. At the end of IT, 140 patients had undetectable inhibitor titers, including 128 who also had normal FVIII kinetics. The remaining 174 patients included 66 with treatment failure, 23 who achieved partial responses, 48 patients in whom treatment was ongoing and 37 with data inadequate to evaluate outcome. Using logistic regression, the best predictive model for success included maximum inhibitor titer, pre-titer, dose and age at treatment. FVIII dose and pre-titer were also associated with treatment duration, as was the time between inhibitor detection and treatment. The risk of relapse was approximately 15% after 15 years of follow-up. INTERPRETATION AND CONCLUSIONS: This study underscores the importance of starting IT as early as possible, at the lowest inhibitor titer and with high FVIII doses in order to maximize the chance of treatment success and minimize treatment costs.

Adolescent↗

Hippocampal perfusion in mild Alzheimer's disease.

Perfusion and metabolic studies in patients with Alzheimer's disease (AD) have so far yielded conflicting results on the functional status of the hippocampal region, whose deep location in the brain makes it critical to optimize the image-reconstruction technique employed in emission tomography. We used a brain-dedicated device (CERASPECT) to perform single photon emission computed tomography (SPECT) studies with 99mTc-hexamethylpropylene-amine-oxime in 22 consecutive patients (mean age: 74+/-6.5 years) with mild [mini-mental status examination (MMSE) score > or =15, mean 20.8+/-3.2], probable AD. The control subjects were 11 healthy elderly people (mean age: 70.5+/-6.5 years). In patients, the total score on the selective reminding test (SRT) was used as an index of memory function. Counts from a hippocampal and a temporoparietal region of interest in each hemisphere were referred to the average thalamic counts. To optimize SPECT images, we used conventional filtered back-projection (FBP) reconstruction and a new iterative method of conjugate gradients (CG), which takes into account the geometrical and physical characteristics of the gamma-camera. Hippocampal perfusion in the two hemispheres was significantly lower in patients than in control subjects, regardless of which reconstruction method was used, and correlated with the MMSE score. The correlation between hippocampal perfusion and the SRT score was significantly (bootstrap procedure) higher with the CG method than with the FBP method (CG: r=0.52 and 0.54; FBP: r=0.39 and 0.47, for the right and left hemisphere, respectively). These results show hippocampal hypoperfusion in patients with mild AD, a correlation between hippocampal perfusion and the severity of cognitive impairment, and enhanced identification of these subtle perfusional changes with the use of an alternative image-reconstruction method that improves the spatial resolution of SPECT images.

Aged↗

Pattern of lymphatic drainage to the sentinel lymph node in breast cancer patients.

BACKGROUND AND OBJECTIVE: We performed a pilot study on 30 consecutive patients undergoing sentinel node (sN) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm. METHODS: There were 6 groups of 5 patients; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN. RESULTS: "False" sN were detected only in patients who had a second injection of radiotracer away from the tumor site; this occurred in 2 of 5 patients (40%) in group I, in 3 of 5 patients (60%) in group II, in all patients in group III, and in 3 of 5 patients (60%) in group IV. The different route of injection (peritumoral or subdermal) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN. CONCLUSIONS: Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin, which indiscriminately drains all quadrants of the breast, like "a neck of a bottle." This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals.

Adult↗

Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero.

Charcot-Marie-Tooth disease type 1 B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (P0) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution in P0ex. In both pedigrees, the mutation caused a late-onset, relatively mild CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the two index cases revealed an identical chronic demyelinating and remyelinating neuropathy dominated by focal foldings of the myelin sheath shaped either as tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P0ex associated with focally folded myelin and provides strong evidence that such a structural alteration of the myelin sheath reflects a distinct pathogenetic mechanism in a subgroup of CMT1B.

Amino Acid Substitution↗

Evaluation of effective renal plasma flow with I-127 ortho-iodohippurate and I-123 ortho-iodohippurate in rabbits.

RATIONALE AND OBJECTIVES: Radiolabeled ortho-iodohippurate is commonly employed for evaluating effective renal plasma flow (ERPF) by means of either in vivo scintigraphy and/or plasma clearance curves. A new method has recently been developed for measuring levels of stable iodine (iodine-127) in biologic samples, based on the detection of x-ray fluorescence photons. In this study, the authors assessed the potential of the new system to evaluate ERPF by using an iodinated contrast medium with adequate glomerular filtration and tubular secretion properties. MATERIALS AND METHODS: A commercial system was used to evaluate ERPF after intravenous injection of stable I-127 ortho-iodohippurate. The results were compared with the clearance values of I-123 ortho-iodohippurate, considered the reference standard. Seven rabbits under general anesthesia were given intravenous injections of I-123 ortho-iodohippurate and I-127 ortho-iodohippurate. The corresponding plasma curves were evaluated from 4 to 60 minutes to calculate ERPF as the dose/integral of plasma curve. RESULTS: The initial distribution volumes of I-123 ortho-iodohippurate (149.4 mL/kg +/- 12.1) and I-127 ortho-iodohippurate (148.8 mL/kg +/- 11.8) were virtually superimposable, thus confirming the chemical identity of the two compounds. The plasma clearance values for I-127 ortho-iodohippurate (11.15 mL/min kg(-1) +/- 1.44) were slightly (not significantly) higher than those for I-123 ortho-iodohippurate (10.49 mL/min kg(-1) +/- 1.41), perhaps because of a relative "mass" load effect of the iodinated medium. CONCLUSION: The results obtained in this study demonstrate the feasibility of the new system for evaluating ERPF, provided that a compound with adequate glomerular filtration and tubular secretion properties is employed.

Animals↗

28. Accuracy of Qualitative and Semiquantitative Analysis of 18FDG Positron Emission Tomography Scans in the Evaluation of Primary and Metastatic Lesions.

Background: 18FDG PET scans are often interpreted on the basis of visual estimation of regional tracer uptake. Whether semiquantitative analysis may help clinicians in the recognition of neoplastic masses still remains debated.Materials and Methods: 134 patients with 144 dubious lesions on CT scans (89 pulmonary, 16 hepatic, 39 soft tissue) were studied by means of PET and 18(F)fluorodeoxyglucose. PET images were qualitatively interpreted by the consensus of two nuclear physicians. Standardized uptake value (SUV) and SUV lean were quantified in both normal and suspicious tissues. SUVs results in the lesion were also expressed as normalized values for the normal mean value in each organ (SUVs/org) and for the overall mean value in normal tissues (SUVs/norm).Results: All patients underwent cytological and/or hystological evaluation of the lesions: 53/144 (37%) were recognized as negative while 91/144 (63%) as positive for primary or metastatic disease. Qualitative analysis resulted in 75% specificity and 93% sensitivity. SUVs, SUVs lean, SUVs/org and SUVs/norm resulted significantly (p < 0.001) higher in positive than in negative lesions by cytology/histology. ROC curves analysis provided optimal cut-off values of 2.5, 0.8, 2.5 and 3, for SUVs, SUVs lean, SUVs/org and SUVs/norm, respectively. Using these cut-offs, specificity and sensitivity resulted 90 and 94%, 83 and 97%, 88 and 93%, 94 and 93%, respectively.Conclusion: Our data suggest that, in patients with CT scan suspicious lesions, visual analysis of PET scans is affected by a high number of false negative results. Semiquantitative assessment of regional metabolic activity has an incremental value and should be used in PET scan interpretation of dubious lesions.

Journal Article↗

Five-day infusion fluorouracil plus vinorelbine in women with breast cancer previously treated with anthracyclines and paclitaxel.

UNLABELLED: The continuous infusion of fluorouracil presents a superior pharmacological profile than its bolus administration, while vinorelbine is a new drug associated with good clinical activity in pretreated metastatic breast cancer. We investigated the combination of this two antitumor drugs with the aim to determine a tolerant and active second-line therapy in metastatic pretreated patients. PATIENTS AND METHODS: Fifty six patients pretreated with chemotherapy received a median of six cycles [2-11] of fluorouracil, 700 mg/m2 for 5 day-continuous i.v. infusion and vinorelbine, 20 mg/m2 on days 1 and 6, every three weeks. The inclusion and evaluation criteria required measurable disease by conventional clinical and/or instrumental means. FINDINGS: Iatrogenic toxicity in 340 administered cycles was mild: stomatitis = 11% (Grade 3 = 5%), constipation and abdominal pain = 12%, G2 neutropenia = 4%, G1 thrombocytopenia = 0.5%. In nine cases moderate infections occurred and six women experienced catheter related complications. Complete and partial remissions were observed in 12% and 36% of evaluable patients, respectively. In particular major tumor regression was documented in 28% of anthracyclines or taxol unresponsive cases. CONCLUSIONS: This drug combination is active in metastatic pretreated breast cancer patients and devoid of serious iatrogenic toxicity. Although it deserves future optimization, for instance with the inclusion of oral fluoropirimidines, it represents a good choice for second-line or non cross-resistant regimens.

Adult↗

Mapping sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue-dye, and intraoperative gamma-probe.

The purpose of the present work was two-fold: 1) to evaluate the predictive value of the sentinel lymph node (sLN) versus the axillary-node status in patients with T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial in which one group of patients with non-metastatic sLN will not have axillary dissection. Of a group of 284 patients considered for this analysis, 264 had a T1 cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18 hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids (particle size between 50-80 nm) was injected subdermally at the cutaneous projection of the tumor. Static gamma-camera images were acquired every 10-15 minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma-probe and by the dye method. The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological and immunohistochemical examinations. The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing standard axillary dissection irrespective of the sLN status. Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement (13.7% false-negative rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN. There was a high, but not absolute, correlation between a negative sLN and a negative axilla.

Adult↗

Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

Adenocarcinoma, Follicular↗

Evidence of cerebral hypoperfusion in scleroderma patients.

OBJECTIVES: To investigate regional cerebral blood flow by (99m)Tc-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT) in a series of 40 patients (mean age 58.5+/-11.5 yr) affected by systemic sclerosis (SSc) in comparison with age-matched healthy controls. METHODS: Subjects affected by concomitant severe pathologies that might interfere with the interpretation of the SPECT results were excluded. SPECT findings were correlated with the severity of peripheral microvascular involvement, as assessed by nailfold videocapillaroscopy (NVC). Whenever possible, patients underwent magnetic resonance imaging (MRI) of the brain. RESULTS: Twenty-one SSc patients (52%) showed hypoperfusion in two or more regions of interest (ROIs) at the SPECT analysis. MRI was available in 14 of these patients, and was shown to be altered in eight of them (57%). One patient with both abnormal SPECT and abnormal MRI was affected by mild cognitive impairment. Transcranial Doppler sonography was normal in all but one of these patients with hypoperfusion. Nineteen patients exhibited a normal brain SPECT scan, but the MRI was shown to be altered in 3/12 of them (25%). No significant differences were found between the group of SSc patients showing hypoperfusion and those showing a normal SPECT scan regarding age, the duration of disease, the presence of vascular risk factors or damage of other organs typically involved in the disease, and the severity of peripheral microvascular involvement (NVC). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion was found in more than half of the neurologically asymptomatic SSc patients studied, paralleling the incidence of altered brain MRI. The hypoperfusion was not linked to ageing and possibly reflects the cerebral location of the microangiopathic process characterizing the disease.

Adult↗

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients.

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.

Antineoplastic Combined Chemotherapy Protocols↗

Experimental model for studying the effects of 2-ethylhexyl-phthalate and dialysate on connective tissue.

In order to have a model for studying the possible implications of 2-ethylhexyl-phthalate and dialysate on connective tissue, we evaluated their direct effects on the air pouch lining tissue and on fibroblast cultures. Air pouches were formed on the backs of 60 ten-week-old Wistar rats by subcutaneous injections of 10 ml sterile air. On the tenth day 2 ml sterile air, or 2 ml 5 microg/L or 2 ml 10 microg/L 2-ethylhexyl-phthalate in olive oil, or 2 ml olive oil alone, or 2 ml 5 mg/ml or 12 mg/ml lyophilized dialysate were injected into the air pouches. After sampling at seven or twenty-one days, the rats were killed. The biochemical data showed an increase in sulphated glycosaminoglycans with 2-ethylhexyl-phthalate and dialysate. Electron microscopy findings revealed cellular alterations such as vacuolation and cell remnants with 2-ethylhexyl-phthalate, while the cells of the air pouches treated with dialysate showed regular organelles with increased and dilated cisternae of rough endoplasmic reticulum. Moreover, an increase in collagen fibres surrounding the damaged zones was noticed in 2-ethylhexyl-phthalate and dialysate treated rats. The glycosaminoglycan modifications and collagen fibre increase seem to suggest that the morphological changes, with the features of fibrosis, could be the result of 2-ethylhexyl-phthalate and dialysate action on connective tissue. Moreover, the air pouch technique can be considered a good model for studying the direct effects of 2-ethylhexyl-phthalate and other substances, such as uremic toxins, on connective tissue.

Animals↗