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Biomedical subjects

E Massa

Publications and source records attributed to E Massa.

52 records · Page 3Linked to original sources

Oral iron absorption in infantile protein-energy malnutrition.

The ability of infants with protein-energy malnutrition to absorb iron was assessed using the serum iron response to a dose of ferrous sulfate providing 3 mg elemental iron per kg body weight. Responses were grouped as flat (delta serum Fe less than 30 microgram/dl), intermediate (30 to 100 microgram/dl), and normal (greater the 100 microgram/dl). Of 25 consecutively admitted children studied, seven had a flat, five an intermediate, and 13 a normal curve (mean delta serum Fe: 10 microgram/dl, 66 microgram/dl, and 175 microgram/dl, respectively). There were no differences among the three groups in hematocrit, fasting serum iron or transferrin saturation, severity of malnutrition, or evidence of other malabsorption sufficient to explain these differences. Although hematocrits, fasting serum iron, and transferrin saturations did not change appreciably during nutritional rehabilitation, all children with initially abnormal responses subsequently had normal tests.

Absorption↗

[Reopening of ventricular septal defect after surgical repair: experience with 7 reoperated patients (author's transl)].

Reopening of ventricular septal defect after surgical repair was investigated -- from six months to five years after operation -- on 75 patients who had undergone closure of ventricular septal defect and on 65 patients who had undergone complete correction of tetralogy of Fallot. The complication appeared in 3 patients (4%) of the first group and in 4 (6%) of the second group, always early after the operation (from 24 hours to 2 months). All patients underwent reoperation - operative mortality rate was 66% in the first group and 25% in the second one. Operative mortality was higher in patients with cardiac and/or tricuspidal failure, also after prolonged preoperative medical treatment.

Adolescent↗

Spiked metallic washer and screw for reattachment of the Achilles tendon after repair of a distal rupture.

The authors review Achilles tendon ruptures and treatment options for the acute and chronic rupture. A case is described involving reattachment of a chronic distal Achilles tendon rupture repair with a spiked metal washer and fully threaded cannulated cancellous screw. Spiked metal washers and their effects on soft-tissue pullout strength, and possible complications are discussed. In review of the literature, the authors have not found this type of fixation used to anchor the Achilles tendon, and feel it may be a viable option when faced with distal Achilles reattachment for the acute and chronic rupture.

Achilles Tendon↗

Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer.

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.

Adult↗

Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment.

OBJECTIVE: So far, it is not well established whether oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. Serum levels of proinflammatory cytokines and IL-2 were also investigated. All these parameters were studied in relation to the clinically most important index of disease progression, namely Performance Status (ECOG PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity, and the reduction of serum levels of IL-6 and TNF. DESIGN, SETTING AND SUBJECTS: We carried out an open non randomized study on 28 advanced stage cancer patients (stage III, 10.7%, and stage IV, 89.3%) with tumours at different (8) sites: all were hospitalized in the Medical Oncology Dept, University of Cagliari Interventions. The patients were divided into 5 groups and a different antioxidant treatment was administered to each group. The selected antioxidants were: alpha lipoic acid 200 mg/day orally, N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally, amifostine 375 mg/day i.v., reduced glutathione 600 mg/day i.v., vitamin A 30000 IU/day orally plus vitamin E 70 mg/day orally plus Vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. RESULTS: Our results show that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels and 2 of them (cysteine-containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the "antioxidant treatment" was found to have an effect both on reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced serum levels of IL-6 and TNF. Patients in both ECOG PS 0-1 and ECOG PS 2-3 responded to antioxidant treatment.

Adult↗

Medroxyprogesterone acetate and megestrol acetate reduce cisplatin-induced serotonin release from human peripheral blood mononuclear cells of cancer patients.

In the present study we evaluated the ability of either medroxyprogesterone acetate (MPA) or megestrol acetate (MA) to reduce cisplatin (CDDP)-induced serotonin (5-HT) release from peripheral blood mononuclear cells (PBMC) of cancer patients. Sixteen patients with cancer of different sites, all in advanced stage of disease, were studied (10 for MPA and 6 for MA). The levels of 5-HT in culture supernatants of PBMC stimulated with CDDP were higher than controls (100 nM vs 51 for MPA study and 123 vs 64 for MA study) and were in the same range of PHA-stimulated PBMC. The addition into cultures of MPA or MA was able to significantly reduce the CDDP-induced production of 5-HT (62 nM for MPA, and 46 for MA study). MPA as well as MA are able to inhibit 5-HT production and/or release by CDDP-stimulated PBMC of cancer patients: this finding to our knowledge has not been previously reported. The concentrations of MPA and MA used in cultures were in the same range as those raised in plasma following the clinical administration of daily doses of 1,000/2,000 mg of MPA and 320 to 960 mg of MA.

Aged↗

Relationships betxween Fas expression, activation molecule CD25, and functional activity of tumor-associated lymphomonocytes from neoplastic effusions.

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.

Adult↗

Assessment of the efficacy of two dosages and schedules of human recombinant erythropoietin in the prevention and correction of cisplatin-induced anemia in cancer patients.

Despite the numerous studies demonstrating the effectiveness of epoetin á (human recombinant erythropoietin) versus placebo in cisplatin-induced anemia of cancer patients, data are lacking on the most effective doses and schedules of administration of epoetin á in this setting. The aim of the present study was to assess the best dose and schedule of administration of epoetin á in cancer patients with cisplatin-induced anemia. This was an open, randomized, single-institution phase II study comparing the ability of two doses and schedules of epoetin á of preventing and/or correcting anemia, measured as the increase in hemoglobin level and decrease in transfusion requirements, in 20 chemotherapy-naive patients with advanced stage head and neck, esophageal, and lung cancer, treated with cisplatin at doses 80 mg/m2. The secondary endpoint of the study was to assess the serum levels of certain cytokines involved in cancer anorexia/cachexia syndrome. The eligible patients were randomly assigned to treatment with either: a) subcutaneous epoetin á 150 U/kg three times a week for up to 12 consecutive weeks (Group A); b) subcutaneous epoetin á 50 U/kg daily for up to 12 consecutive weeks (Group B). The following laboratory parameters were assessed before the study entry and during the study: hemoglobin (weekly); serum iron, transferrin and ferritin (before entry). The following immunological parameters were assessed before and after study end: Interleukin (IL)-1á, IL-1 , IL-6 and Tumor Necrosis Factor (TNF) á. Twenty patients were enrolled, data were available for 17. Nine patients were assigned to Group A and 8 to Group B. No statistically significant difference of hemoglobin level was found between the 2 groups at baseline, at month 1, 2 and 3, neither in the comparison of the change from baseline between the two groups. In Group A fewer transfusions were administered per patient per month after the first month of epoetin á therapy, compared to Group B. No significant difference was found as for transfusion requirements at month 1, 2 and 3 between Group A and B. The epoetin á dose administered was slightly higher than that projected. Epoetin á was well-tolerated. There was no statistically significant correlation between change in hemoglobin level and tumor response for either group, neither between change in hemoglobin level and change in ECOG score from baseline to final was observed. The changes from baseline of IL-1á and IL-1 , IL-6 and TNFá were not remarkable nor univocal in either group, there was not correlation between hemoglobin change and serum cytokine changes from baseline, except for IL-6 in Group A.

Adult↗

Phase II study of induction chemotherapy followed by concomitant chemoradiotherapy in advanced head and neck cancer: clinical response and organ/function preservation.

We planned to conduct a trial of induction chemotherapy followed by concomitant chemoradiotherapy with the goal of organ-function preservation in advanced head and neck cancer patients with the response rate and local control of disease as primary endpoints and the assessment of toxicity as secondary endpoint. The overall treatment plan consisted of 3 cycles, each q. 28 days, of induction chemotherapy with cisplatin, 5-FU, leucovorin and interferon alpha2b (PFL-IFN), followed by response evaluation and local therapy with concomitant chemoradiotherapy with 5-FU, hydroxyurea and concomitant radiotherapy (FHX). The evaluation of clinical response was performed during the 2nd week after the 3rd cycle of induction chemotherapy and FHX was initiated 28 days after the 3rd cycle of induction chemotherapy. Hydroxyurea was administered orally at doses of 1 g every 12 h x 11, 5-FU was administered on days 1 through 5 at 800 mg/m2/d for 5 days. Daily fraction of radiotherapy were administered at 2.0 Gy on days 1 through 5. FHX cycles were repeated every 14 days until completion of radiotherapy. Total radiotherapy doses consisted of 70 Gy. Seventeen patients (mean age 56.53 years, range 40-73, male/female 15/2, site: oral cavity 6, 35.29%; oropharynx 3, 17.6%; hypopharynx 3, 17.65%; larynx 2, 11.76%; paranasal sinuses 2, 11.76%; salivary glands 1, 5.88%; ECOG PS 0/1: 10/7, stage: III/IV 3/14) were enrolled from January 1998 to August 1998. All 17 patients initiated induction chemotherapy on this protocol. Twelve patients were analyzed for response (5 patients were not evaluable): 2/12 (16.7%) patients achieved a CR and 10/12 (83.3%) achieved a PR for an ORR of 100%. Concomitant chemoradiotherapy was administered on protocol to 10 patients: 4 patients (40%) had CR, 3 patients (30%) had PR >/=70% for an ORR of 70%, 1 patient (10%) had SD and 2 patients (20%) had PD. As for local therapy, according to treatment plan, of the 8 eligible patients who completed chemoradiotherapy, the 4 patients with CR were submitted to random biopsies, which resulted histologically negative, the 3 patients with PR >/=70% underwent conservative organ-preserving surgery, the patient with SD underwent salvage surgery, preserving voice. Thus, organ-preservation was achieved in all 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 3 patients only conservative surgery. Overall, after completion of all therapy, 6/8 (75%) patients were rendered disease-free. Both induction chemotherapy and concomitant chemoradiotherapy resulted in significant toxicity, which consisted mainly of mucositis and thrombocytopenia. In conclusion, in the present study we have achieved a good clinical response and an optimal organ preservation, at the cost of a severe toxicity.

Adult↗

Prevention of nausea and vomiting (N&V) in cancer patients receiving high-dose cisplatin. Assessment of the potential antiemetic activity of transdermal fentanyl (TTS-F) compared to standard antiemetic treatment in acute and delayed N&V: first clinical report.

UNLABELLED: A single-institution, prospective, open crossover study was performed to compare the effectiveness and tolerability of transdermal fentanyl (TTS-F) vs intravenous (i.v.) ondansetron (OND), both combined with i.v. DEX, in the prevention of acute nausea and vomiting (N&V), and TTS-F vs metoclopramide (M), both combined with intramuscular (i.m.) DEX, in the prevention of delayed N&V in patients with advanced stage head and neck squamous cell carcinoma receiving high-dose (> or = 100 mg/m2) cisplatin. This is the first report on the clinical use of TTS-F in this setting. PATIENTS AND METHODS: All patients were adequately informed of the study characteristics and gave their written informed consent before study entry. The antiemetic treatment for acute N&V consisted of A) OND 8 mg plus DEX 20 mg (i.v.) or B) TTS-F 75 micrograms/h plus DEX 20 mg i.v. For prevention of delayed N&V, patients receiving TTS-F for acute N&V were given TTS-F at the same dosage (75 micrograms/h) on days 2-5, whereas patients receiving OND for acute N&V were treated with M 20 mg orally every 6 h on days 2-5, starting 24 h after CDDP. All patients received DEX 8 mg i.m. every 12 h on days 2 and 3, 4 mg i.m. every 12 h on days 4 and 5, starting 24 h after CDDP. From November 1997 to April 1998, 15 consecutive patients entered the study and were assigned to one of the two alternative treatments for acute N&V. All of them were evaluable. Twelve patients were evaluable for delayed N&V. Seven patients were assigned to Group 1 starting with treatment A (OND + DEX) and 8 patients were assigned to Group 2 starting with treatment B (TTS-F + DEX). In the prevention of acute N&V, the overall efficacy of OND + DEX was statistically significantly higher than that of TTS-F + DEX in achieving Complete Response (CR) and Major Efficacy (ME = CR + Major Response, MaR). As for delayed N&V, the overall efficacy of M + DEX, both in achieving CR and ME, although higher, was statistically not significantly different from that of TTS-F + DEX. Unfortunately, due to the small number of patients included in the study, the sophisticated criteria for evaluating response in antiemetic research, such as the persistence of efficacy, the response after crossing-over, did not make it possible for us to draw additional conclusions, although the trend was in favor of "standard" treatments, particularly in acute N&V. The 'response to treatment A (OND + DEX) in the prevention of acute N&V was in the same range as the response to treatment A (M + DEX) for delayed N&V. The response to treatment B (TTS-F) for acute N&V was lower than the response to the same treatment for delayed N&V. The TTS-F treatment was well-tolerated with no significant side-effects including the well-known opioid-related symptoms. Our study confirms that the currently available standard antiemetic treatments both for acute and delayed N&V must be considered by far the most effective ones for clinical use.

Administration, Cutaneous↗

Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer, pre-treated with chemotherapy.

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.

Adenocarcinoma↗