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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 109 records · Page 6Linked to original sources
PubMed2000

Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study.

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients' main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin's disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.

Adult↗
PubMed2000

Radiation injury involving the internal carotid artery. Report of two cases.

Radiation therapy is an uncommon cause of stenosis and occlusions of the cervical internal carotid artery (ICA). We describe two cases of cerebral ischemia due to ICA stenosis in patients irradiated for malignant tumors (lymphoma and breast cancer). The first patient, a 32-year-old man, presented with an episode of cerebral ischemia. Six years previously he had received irradiation therapy for a left laterocervical mass histologically diagnosed at biopsy as a Hodgkin's lymphoma. Cerebral angiography on entry revealed bilateral occlusion of the cervical ICA, with a 2-cm stump at the origin of the left ICA. Despite anti-platelet aggregation therapy the ischemic attacks persisted, necessitating a stumpectomy. After vascular-repair surgery the patient had no further ischemic symptoms. The second patient, a 42-year-old woman, began to experience the sudden onset of pain in the right arm and left hemiparesis five years after surgery plus irradiation (4500 rad) for breast cancer, and three years after excision of a single cerebral metastasis. Cerebral angiography obtained on admission showed occlusion of the right ICA and right subclavian arteries, both lesions necessitating thrombectomy. After surgery the right radial pulse immediately re-appeared and the hemiparesis regressed. In both patients, 2-year follow-up assessment by Doppler ultrasonography and magnetic resonance angiography (MRA) confirmed that the operated arteries remained patent. These two unusual cases underline the potential risk of irradiation-induced ischemic cerebrovascular symptoms, suggesting that patients who have received radiation therapy to the neck and mediastinum who survive for more than 5 years should undergo regular non-invasive imaging of neck vessels (Doppler ultrasonography and MRA).

Adult↗
PubMed2000

Clinical characteristics of adolescent headache.

We evaluate clinical characteristics of headache in a group of subjects > 12 years to assess the sensitivity and specificity of the IHS criteria. We consider whether age at onset may influence the clinical features. We used a semi-structured questionnaire to examine 136 patients consecutively referred to our division. We considered the following subdiagnoses: IHS 1.1, 1.2, 1.7, 2.1, 2.2, 2.3. Migrainous disorders were found to be more common than non-migrainous headaches. A definite diagnosis was established in 68.1% of the migrainous group and in 86.6% of the tension-type headache group. Unilateral location, severe intensity of pain, the presence of nausea, vomiting, phonophobia and photophobia were features which differed between migrainous and non-migrainous subjects. No difference was found regarding aggravation of the headache by physical activity. On the basis of the criterion duration of attacks < 2 hours, IHS 1.7 was found to differ significantly from other migraine types. With the exception of the presence of vomiting in migrainous patients, the age at onset was not found to be a factor influencing the characteristics of the headache. Diagnostic criteria for migraine were highly specific but poorly sensitive, and those for tension-type headaches highly sensitive but less specific. The sensitivity/specificity of the IHS criteria in adolescent migraine can be influenced by the heterogeneity of the clinical characteristics. In fact, the intensity, the location and the quality of pain were similar to those found in childhood migraine, while the concomitant symptoms were less frequent than in childhood and in adult migraine. Further studies are needed to define the degree of severity of the clinical features in adolescent headache and to address the question of the validity of the IHS criteria.

Adolescent↗
PubMed1999

Cavernous angiomas of the brain stem. Intra-axial anatomical pitfalls and surgical strategies.

BACKGROUND: We review the surgical anatomy of the brain stem in relation to the surgical approaches adopted for treatment of cavernomas and identify possible "safe entry zones" on the anterior face of the brainstem. METHODS: Twelve symptomatic patients with cavernoma or telangectasia of the brain stem were surgically treated. The brain stem was divided into the following anatomical areas: ventral medulla, dorsal medulla, dorsal pons, ventral pons, ventral mesencephalon, and dorsal mesencephalon, so that the surgical approach could be "individualized" according to the position of the cavernoma, the nerve fasciculi and nuclei. RESULTS: On the anterior surface of the brain stem a medullar paramedian oblique access to the anterolateral sulcus and a paramedian sagittal pons access seem to avoid the main nerve fasciculi and nuclei. CONCLUSIONS: Although the parenchymal window produced by the cavernoma is the most important parameter for the choice of approach, fairly safe entry zones may be identified even on the anterior surface of the medulla and pons.

Adult↗
PubMed1999

Dose-escalation of CHOP in non-Hodgkin's lymphoma.

BACKGROUND: CHOP is considered to be the gold standard for patients with histologically aggressive non-Hodgkin's lymphoma both in limited and advanced stages. In order to determine the maximum tolerable dose of an intensified CHOP regimen, a dose-escalation study of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with non-Hodgkin's lymphoma (NHL) was started. PATIENTS AND METHODS: With an increased fixed dose of doxorubicin at 75 mg/m2 instead of 50 mg/m2 on day 1 and standard doses of vincristine (1.4 mg/m2 on day 1) and prednisone (100 mg day 1 through 5), cyclophosphamide dose was escalated by increments of 250 mg/m2 in consecutive cohorts of at least three patients starting from 1000 mg/m2. Granulocyte-colony stimulating factor (G-CSF) support was added to the regimen starting from the dose-level inducing grade 4 neutropenia lasting more than five days in two patients. Dose limiting toxicity was defined as either the dose inducing grade 4 neutropenia lasting more than seven days despite the use of G-CSF, or grade 3-4 thrombocytopenia lasting more than seven days, or any grade 4 non-hematological toxicity other than alopecia. The dose-level below the one inducing dose-limiting toxicity was defined as maximum tolerable dose. All patients were treated on an outpatient basis. Dose-intensity parameters for single agent doxorubicin and cyclophosphamide as well as for the whole regimen were evaluated. RESULTS: Eighty-seven patients are evaluable over a four-year study period. At 1750 mg/m2 dose-level, G-CSF was added to the regimen according to described criteria. At the cyclophosphamide dose of 3000 mg/m2, dose-limiting hematological toxicity occurred in two patients, with one grade 4 thrombocytopenia and neutropenia and one grade 4 neutropenia lasting more than seven days. Thus, cyclophosphamide dose of 2750 mg/m2 was defined as maximum tolerable dose. CONCLUSIONS: CHOP intensification of approximately 1.8 times that of the standard regimen is feasible and safely administered on an outpatient basis with G-CSF support. Further investigation on the role of dose-intensity in the outcome of NHL should focus on the comparison of intensified CHOP regimen and standard CHOP or high-dose chemotherapy.

Adolescent↗
PubMed1999

p16 (INK4a, MTS-1) gene polymorphism and methylation status in human pituitary tumours.

OBJECTIVE: The p16 gene, which encodes a physiological inhibitor of the cyclin D-CDK4 complex, is now considered as an important tumour-suppressor gene in a variety of tumours. A marked reduction of its expression has been reported to occur without significant genetic alterations in human pituitary adenomas, although rare point mutations of uncertain functional significance have been described. On the other hand, p16 gene silencing due to hypermethylation has been reported in several human primary tumours. The aim of this study was to further investigate the pathogenetic events leading to p16 gene inactivation in pituitary tumours. DESIGN: To screen a european series of human pituitary tumours for p16 gene alterations and possible gene hypermethylation. PATIENTS: A representative series of 31 human pituitary tumours-30 macroadenomas, including a MEN-1 non-secreting pituitary adenoma and a non-MEN-1 familial giant GH-secreting adenoma, and one FSH-secreting pituitary carcinoma-was studied. METHODS: Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for p16 gene alterations in all cases. Direct sequencing of PCR-products was obtained by the di-deoxynucleotide method where suspected abnormalities of the PCR-SSCP analysis were observed. In 24 samples, a methylation-specific PCR assay (MSP-PCR) was used to determine p16 gene methylation status. RESULTS: Two sporadic cases of pituitary adenomas had a similar single A to G base substitution leading to an heterozygous Ala140Thr p16 polymorphism, which has not previously been described in such tumours, but is known to be functionally silent. No other p16 abnormality could be suspected from PCR-SSCP analysis in this series. In contrast, the presence of methylated-specific PCR products was observed in 20/24 cases (83.3%). CONCLUSIONS: This study confirms that p16 gene mutations are not involved in the pathogenesis of human pituitary tumours, although polymorphisms can be demonstrated, depending on the population considered. In contrast, the high incidence of hypermethylation of the p16 gene suggests that such an alteration occurs early in pituitary tumours, and may play a role in pituitary tumorigenesis.

Adenoma↗
PubMed1999

Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch.

BACKGROUND: A new estradiol transdermal patch was developed for a once weekly application, with the aim to achieve an optimum practicability and to improve long-term compliance with estrogen replacement therapy. The pharmacokinetics of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during a 7-day application of the new patch is reported in this publication. METHODS: Unconjugated estradiol and estrone were assayed in plasma in a three-way crossover study on 18 postmenopausal women during and after a 7-day application of 3 strengths of the new patch, with daily release rates of 25, 50 and 75 micrograms of estradiol. RESULTS: During the 7-day application of the transdermal patches the concentration in plasma of unconjugated estradiol increased from less than 5 pg/ml, typical of postmenopause, to average concentrations of 26, 49 and 66 pg/ml under the patches with the release rates of 25, 50 and 75 micrograms/day of estradiol, respectively. The increases were linearly related and proportional to the strength of the patches. Upon removal of the patches, the estradiol concentrations returned to the basal postmenopausal values in 8-24 h. Retarded with regard to estradiol, there was also an increase of unconjugated estrone, from basal concentrations of 24 pg/ml to average concentrations of 39, 54 and 62 pg/ml, respectively. Estrone returned to its basal concentrations 24-48 h after removal of the patches. The estradiol/estrone ratio from the low pre-treatment values of 0.15-0.21 typical of postmenopause increased to average values of 0.51, 0.92 and respectively 1.09 during the application of the patches with the three strengths. The ratios are in the range of those of unconjugated hormones during the fertile age of women. The patches were well tolerated by the skin, with rare mild and transient reactions that disappeared spontaneously and did not cause interruption of treatment. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol found especially under the application of the two higher strengths, i.e. with release of 50 and 75 micrograms/day of estradiol. CONCLUSIONS: The effective pharmacokinetic performance over the 7-day application, combined with the good general and local tolerability and the need to apply the patches only once weekly confer to the new patches a favorable practicability for the long-term estrogen replacement therapy needed to control the most severe postmenopausal disorders.

Administration, Cutaneous↗
PubMed1999

Spontaneous occlusion of supraclinoid aneurysms after the creation of extra-intracranial bypasses using long grafts: report of two cases.

OBJECTIVE: We describe two cases of giant supraclinoid aneurysms, treated by means of saphenous vein grafting between the external carotid artery and the middle cerebral artery, which unexpectedly spontaneously occluded. CLINICAL PRESENTATION: Two patients presented with subarachnoid hemorrhage and headache, respectively. In the first case, angiography showed an aneurysm of the right internal carotid artery (ICA), which had been treated by clipping. Repeat angiography showed a giant aneurysm of the right ICA, the formation of which was probably caused by sliding of the clip that had been applied during the previous operation. The patient was operated on again, but it was impossible to exclude the aneurysm because no clear neck could be identified. In the second case, magnetic resonance imaging and cerebral angiography showed a large, partially thrombosed aneurysm of the supraclinoid segment of the left ICA. TECHNIQUE: In view of the patients' ages and the statuses of compensatory circulation, each patient underwent cerebral revascularization with a long saphenous vein graft placed between one branch of the middle cerebral artery and the external carotid artery, in anticipation of subsequent endovascular treatment of the aneurysm and/or closure of the ICA in the neck. Postoperative angiography demonstrated spontaneous occlusion of the aneurysms. CONCLUSION: Thrombosis of an aneurysm may occur spontaneously or after explorative surgery. However, it should be remembered that spontaneous occlusion of an aneurysm may be induced or favored by hemodynamic vascular alterations that take place inside the aneurysm after a high-flow extra-intracranial bypass has been created.

Adult↗
PubMed1999

Management of anal cancer: our experience.

The aim of this report was to relate our experience in the management of anal cancer. Up to now, the standard treatment reported in the literature for this particular disease is combination chemo-radiotherapy in most patients. Management decisions such as radical chemotherapy, surgical resection for poor response or relapses are frequently modified by some factors such as disease stage, social and psychological status of the patient, age-associated comorbidity factors. From 1992 to 1998, 24 consecutive patients (median age: 64 years) with untreated epidermoid carcinoma of the anus (T2, 58%; T3, 42%; N+, 25%) were treated, as first-line therapy, with a simultaneous chemo-radiotherapy combination. The crude mortality rate was 34%, with 29% dying of their disease. The stage distribution and the amount of chemo-radiotherapy administered were not age-limited but younger patients had more surgery and suffered less toxicity with a greater proportion remaining alive and disease-free. These data suggest that a more aggressive multi-modality approach may improve disease-free response and survival.

Adult↗
PubMed1999

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.

Adult↗