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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 37 records · Page 2Linked to original sources
PubMed2005

Online convective therapies: results from a hemofiltration trial.

With the introduction of the on-line preparation of dialysis fluids, the hemofiltration technique, which has never had a widespread diffusion in its old version with the infusion bags, has gained a new interest. We planned a prospective, randomized, 3-year-long study comparing survival and morbidity in ultrapure bicarbonate dialysis (BD) with on-line predilution hemofiltration (HF). Since comorbidity is one of the main factors limiting survival, the study was addressed to patients with a severe degree of comorbidity. The paper presents the preliminary results of the trial. Sixty-four patients were enrolled and randomized to either BD (N = 32) or HF (N = 32). Mean age and dialysis vintage were comparable. Twenty patients died during the study, 12 in BD and 8 in HF. The relative risk of death was 11% higher in patients treated with BD compared to those in the HF group (p < 0.005). The number of hospitalisation events per single patient was lower, even though not significantly, in HF compared to BD (1.94 + 1.26 in HF vs 2.48 + 1.98 in BD, p = NS). As concerns biochemistry, apart from beta-2-microglobulin, any other substantial difference was not found during the study, though the small solute concentration was generally a little more elevated in HF than in BD. Dialysis hypotension showed a trend to decrease in both the dialysis modalities up to near half of the trial, then, during the last year, it remained quite stable in HF, while, on the contrary, it increased in the BD group. By the end of the protocol, patients in HF showed a 2.5% incidence of acute dialysis hypotension, while patients in BD had 23%.

Aged↗
PubMed2005

Mid-dilution: the perfect balance between convection and diffusion.

Although hemodiafiltration (HDF) offers the advantage of increased convective clearance for middle molecules, there is still controversy as to whether reinfusion should occur pre- or post-filter. Mid-dilution hemodiafiltration (MD HDF) is a new HDF technique that uses a special dialyzer, MD190, which allows both pre- and post-reinfusion. While externally the dialyzer looks similar to conventional hemodialyzers, the internal fibers are divided into two bundles by a special annular header that first lets the blood pass through the peripheral bundle in post-dilution, mix with the reinfusion fluid at the opposite end of the dialyzer and then proceed (after pre-dilution) to the dialyzer blood exit. The dialyzer is able to support substantially higher reinfusion rates (10-12 l/h). We have compared the removal characteristics of several small solutes and larger middle-molecular-weight toxins by examining instantaneous clearance at 45 min, the dialysis reduction ratio and total mass removal (by spilling) in a three-center prospective cross-over study. Twenty patients were randomized to a treatment sequence of one-week high-flux bicarbonate hemodialysis (HD) followed by MD HDF, or vice versa. The parameters evaluated included urea, creatinine, beta2-microglobulin, angiogenin, leptin, retinol-binding protein, and the effects on sodium, potassium, bicarbonate and calcium. Blood flow rates ranged between 300-450 ml/min (mean 359 +/- 44 HD, 367 +/- 35 MD HDF). The mean reinfusion for MD HDF was 166 +/-17 ml/min. MD HDF had a significantly better instantaneous clearance for urea (328 +/- 28 vs 277 +/- 40); creatinine (292 +/- 32 vs. 212 +/- 66); phosphate (324 +/- 38 vs. 242 +/- 63); beta2-microglobulin (249 +/- 27 vs. 100 +/- 24); angiogenin (173 +/- 27 vs. 28 +/- 32); and leptin (202 +/- 29 vs. 63 +/- 43). Treatments were well tolerated with no adverse reactions occurring during any of the treatments. The MD HDF filter's unique configuration is designed to deliver high-efficiency HDF with a significant improvement in small and middle molecule removal. MD HDF supports substantially higher ultrafiltration rates, and as such, results in a higher removal of middle-molecular-weight toxins.

Blood↗
PubMed2005

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED: The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION: It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Adult↗
PubMed2005

Anemia and erythropoietin treatment in chronic kidney diseases.

In patients with renal failure, severe anemia and associated fatigue, cognitive and sexual dysfunctions have a significant impact on the quality of life. Anemia also represents an important etiological factor in the development of left ventricular hypertrophy. An inadequate production of a glycoprotein hormone, erythropoietin (EPO), is the major cause of anemia in presence of a reduction in the glomerular filtration rate. EPO is the primary regulator of the growth and survival of the erythroid progenitor. The treatment of anemia in chronic renal failure has been revolutionized by the introduction of recombinant human EPO. The vast majority of patients responds very well to treatment, although 5-10% of patients shows some resistance to EPO, the most common cause of which is iron deficiency. Several studies have recently been started in order to investigate the effects of preventing renal anemia from ever developing in uremic patients. The hemoglobin concentration target in pre-dialysis and dialysis patients is the subject of continuous re-assessment.

Anemia↗
PubMed2005

Vasospasm of venous grafts in extra-intracranial by-pass. Report of two cases.

Two patients are described, the first with a giant aneurysm of the left carotid bifurcation previously treated by endovascular technique, the second with a bilateral intracavernous aneurysm: both were submitted to high-flow by-pass operation. The first patient was a 40 year-old woman who had presented subarachnoid hemorrhage 6 months before operation. She had been treated by means of a high-flow by-pass between the external carotid artery and the middle cerebral artery. Control angiograms performed 12 hours later showed a stenosis above the suture between the external carotid artery and the venous graft. Angioplasty was performed by endovascular route: new angiograms showed occlusion of the graft while dopplersonography demonstrated the presence of flow within the graft. Angiograms performed 1 week later showed marked vasospasm of the venous graft, of the internal carotid artery, the anterior cerebral artery and the middle cerebral artery. The evolution of spasm of the graft and of the intracranial arterial flow was monitored by dopplersonography and MR-angiography: the latter was performed 20 days after the last angiography and confirmed patency of the graft, while dopplersonography showed resolution of vasospasm. Finally, the aneurysm was embolized. The second patient was a 49 year-old woman with mild left palpebral ptosis and retro-orbital pain. She had already been submitted to high-flow by-pass operation 7 months earlier to treat a right intracavernous aneurysm; the left by-pass was necessary because the intracavernous aneurysm had become symptomatic. One week after surgery, spasm of the venous graft was documented by MR-angiography. In both cases, treatment consisted of calcium antagonists as well as hypertensive and hypervolemic medication, which was successful in treating vasospasm of the venous graft and its symptoms. Spasm of the venous graft, a well-known occurrence in cardiac revascularization, can also be observed in cerebral revascularization.

Adult↗
PubMed2005

Sylvian subarachnoid and extra-pial cavernous angioma.

Cavernous angiomas are one of the four types of vascular malformations of the central nervous system. Lesions situated subarachnoidally are rare although some cases with an infratentorial localization have been reported. Our case represents an unusual localization of a subarachnoid cavernous angioma. A 35- year-old patient was admitted to our department with signs of subarachnoid hemorrhage. A 1 cm hyperdense lesion placed at the right Sylvian fissure was distinguished by CT-scan examination and no arterial supply was revealed on cerebral angiography. Surgical intervention showed a lesion placed extra-pial and totally encased in the subarachnoid space in the superficial part of the Sylvian cistern. This case represents a radiologically visible supratentorial extra-pial subarachnoidal cavernous angioma. This case provides confirmation of one of the supposed causes of subarachnoid hemorrahage ''sine materia''.

Adult↗
PubMed2004

Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer.

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.

Adenocarcinoma↗
PubMed2004

Ochratoxin A and zearalenone: a comparative study on genotoxic effects and cell death induced in bovine lymphocytes.

Ochratoxin A (OTA) and zearalenone (ZEA), two naturally occurring contaminants of animal feed, have been implicated in several mycotoxicoses in farm livestock but there is little information on their genotoxicity and toxicity in these species. Therefore, we investigated on the cytogenetic and cytotoxic effects of both OTA and ZEA in in vitro cultures of bovine lymphocytes. We determined chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic index (MI) and cell viability following OTA and ZEA treatment. This report is the first to provide evidence of a statistically significant increase of structural CAs and of SCEs/cell associated with a reduction of the MI in all OTA- and ZEA-treated bovine lymphocyte cultures and a clear reproducible reducing effect of OTA on cell viability mediated by enhanced apoptosis. OTA-induced programmed cell death was not limited to bovine lymphocytes, as comparable data were demonstrated in the human leukemic T-cell line Jurkat.

Animals↗
PubMed2004

Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients.

Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.

Acromegaly↗
PubMed2004

Role of intensive therapy in liver transplant recipients: experience in blood purification and biosynthetic techniques.

The severity of the clinical situation for patients awaiting liver transplant depends on the conditions induced by the liver disease, which trigger a series of extrahepatic system alterations requiring prompt correction to improve the patient's preoperative condition. In the pre-terminal stage of liver cirrhosis, the patient's general condition is partly due to toxemia caused by loss of blood purification functions and also to liver synthetic deficits. In this study we describe our experience with extracorporeal support techniques, both from the blood purification standpoint and from biosynthesis. This experience represents an historic overview of the techniques involved in for construction of an "artificial liver." The aim of this work was to provide a summary of our clinical findings and current methods in extracorporeal liver support with the goal of improving the clinical status potential transplant patients.

Adolescent↗
PubMed2004

Operative office hysteroscopy without anesthesia: analysis of 4863 cases performed with mechanical instruments.

STUDY OBJECTIVE: To evaluate the efficacy of, and patients' satisfaction with, office hysteroscopic treatment of benign intrauterine pathologies using 5F hysteroscopic instruments. DESIGN: Observational clinical study (Canadian Task Force classification II). SETTING: University center. PATIENTS: Four thousand eight hundred sixty-three (4863) women. INTERVENTION: Office hysteroscopy without analgesia or anesthesia. MEASUREMENTS AND MAIN RESULTS: We used 5F mechanical instruments (scissors, grasping forceps) to treat cervical and endometrial polyps ranging between 0.2 and 3.7 cm, as well as intrauterine adhesions and anatomic impediments. From 71.9% to 93.5% of women underwent the procedure without discomfort for all pathologies treated except endometrial polyps larger than the internal cervical os, for which 63.6% experienced low or moderate pain. At 3-month follow-up, pathology persisted in 364 patients (5.6%). CONCLUSION: Simple instruments enable us to perform many operative procedures in an office setting with excellent patient satisfaction, provided that the indications are correct.

Adolescent↗
PubMed2004

Metabolism of adenosine in human colorectal tumour.

The aim of this work is to analyse the activities of the enzymes metabolising adenosine in fragments of neoplastic and normal-appearing mucosa, surrounding the tumour in 20 patients affected by colorectal cancer. The results show that the activities of the enzymes are markedly higher in tumour in comparison to normal mucosa to coope with the accelerated purine metabolism in cancerous tissues.

Adenosine↗
PubMed2004

Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.

BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program. PATIENTS AND METHODS: To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status < or =2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks. RESULTS: Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild. CONCLUSION: Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.

Adenocarcinoma↗
PubMed2004

Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer.

BACKGROUND: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Women (n=509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 (every 4 weeks) or doxorubicin 60 mg/m2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. RESULTS: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR)=1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR=3.16; 95%CI 1.58-6.31; P<0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR=0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin. CONCLUSIONS: In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.

Adult↗