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Biomedical subjects

J Carles

Publications and source records attributed to J Carles.

At least 19 recordsLinked to original sources

[Experience with 150 subcutaneous venous reservoirs for venous access and infusion for the treatment of adult patients with oncologic and hematologic disorders and acquired immunodeficiency syndrome].

BACKGROUND: In the present study the year experience of a multidisciplinary team (oncologic, unit for the acquired immunodeficiency syndrome, and surgery) with the use of a new method of central intravenous administration of medication such as that of subcutaneous venous reservoirs (SVR) is reviewed. METHODS: The subcutaneous injection capsules were implanted as a venous access in 150 surgical procedures in 146 patients from October 1985 to April 1991 with a total follow up of 29.190 days and a mean length of 251 days for SVR. Sixty-two percent (94 implantations) of the SVR were implanted in the out patient clinic, 20% (30 patients) were admitted for placement of the reservoir although this was only indicated in the first two years of the series, 13% (20 patients) during hospitalization for the base disease and only 4% (6 patients) were specifically admitted for surgical preparation (plasma, platelets, and others). SVR were used for chemotherapy (124 cases, 82%), repeated transfusions (6 cases, 4%) and chronic medication (acquired immunodeficiency syndrome, infections) (30 patients, 20%). Forty-two percent permitted chemotherapy administration by continual transfusion on an out patient regime. RESULTS: A series of mechanical complications (3 cases, 2%), septic (9 episodes in 7 patients, 5%) and thrombotic (8 of the catheter) (5%) and 4 of the central veins (2%) were observed. In the present series the rate of infections (5%) (0.072 episodes of bacteremia per 100 days/patient) and thrombosis (3%) was very low due to a strict protocol of maintenance and control by the medical team and hospital staff. The need for radiologic control during surgery is emphasized although, as demonstrated in the present review, the technique of localization by a cath-finder (external detector) permits greater speed with the same security. CONCLUSIONS: The degree of patient satisfaction and the minimum incidence of serious complications in determined risk groups (neutropenia, acquired immunodeficiency syndrome) demonstrates that subcutaneous venous reservoirs (SVR) constitute an excellent method as a chronic venous access. The SVR present a lower rate of complications if compared with any historic series of external vascular catheterization.

Acquired Immunodeficiency Syndrome

Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer.

Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. Sixteen patients were evaluable for response and toxicity. Myelosuppression was the dose-limiting side effect. Neutropenic fever was observed in eight patients (53%) and stomatitis in six (40%). No patient had a greater than 14% decline in the cardiac ejection fraction. Strict adherence to the dose-schedule designed was impossible as doses were trimmed and delayed in 30% of instances. The overall objective response rate was 81% (95% confidence limits, 62% to 100%), in limited disease there were complete remissions in 57%. With a 16 months median follow-up, overall median survival was 13 months. This study was unable to prove the feasibility of epirubicin escalation when added to etoposide-cisplatin combination, hampering the dose-intensification Norton-Simon model test.

Antineoplastic Combined Chemotherapy Protocols

Phase I study of mitonafide in 120 hour continuous infusion in non-small cell lung cancer.

Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to deliver the maximum amount of drug while avoiding the risk of central nervous system (CNS) toxicity, previously observed in studies with daily short (1 hour) administration schedules. Twenty patients were treated at doses ranging from 107-200 mg/m2 x 120 h. C.I. Dose-limiting toxicity with this schedule of administration was leukopenia. Other toxicities were mild or not relevant. No CNS toxicity was observed. The recommended dose for phase II C.I. Mitonafide studies is 170 mg/m2 x 120 h. C.I. in previously untreated patients. Plasma level monitoring is recommended.

Aged

Comparison of three protracted antiemetic regimens for the control of delayed emesis in cisplatin-treated patients.

Antiemetic activity of three protracted regimens for the control of cisplatin-evoked delayed emesis was explored. 63 patients were randomly assigned to receive one of three protracted antiemetic schedules over 4 days. Group C patients received dexamethasone 8 mg twice daily on days 2 and 3, then 4 mg twice daily on days 4 and 5; in group B, alizapride 2.5 mg/kg four times daily on days 2-5 plus dexamethasone as in group C was administered; and in group A, metoclopramide 0.5 mg/kg four times daily on days 2-5 plus dexamethasone was given at the same dose-schedule as in groups C and B. Complete protection from delayed vomiting was achieved in 44% of group C, 30% of B and 70% of group A (P = 0.02). Mild side-effects were noted in all three groups. A higher complete protection for delayed emesis was obtained in metoclopramide-dexamethasone-treated patients. Neither of the regimens used in the protection of delayed emesis controlled late nausea.

Adult

A phase II study of days 1 and 8 cisplatin and recombinant alpha-2B interferon in advanced non-small cell lung cancer.

Preclinical data from studies of human lung cancer xenografts suggest that the cytotoxic effects of cisplatin are enhanced by alpha-interferon. To verify the above observations, the authors initiated a Phase II trial in advanced non-small cell lung cancer (NSCLC). Cisplatin was given at 100 mg/m2 during a 28-day cycle in a divided day 1 and day 8 schedule. Starting on day 1, alpha-2B interferon was administered intramuscularly at a dose of 5 million units three times a week continuously for a minimum of 2 months. Between January 1989 and September 1989, 30 patients were evaluated for response and toxicity. According to the staging system proposed by Mountain, 20 patients had Stage IV disease, 7 had Stage IIIB disease, and 3 had Stage IIIA disease. Expression of neuron-specific enolase (NSE) and Leu-7 was immunohistochemically investigated to evaluate possible relationship to treatment response. The response rate was 13.3% (95% confidence interval [CI]: 1.2% to 25%). The four responders showed positivity for NSE, and two of them were positive for Leu-7. An average of three cycles was given. The mean dose intensity administered was 83% of the projected dose for cisplatin and 92% of the projected dose for alpha-2B interferon. A standard scale was used to assess interferon toxicity. Hematologic, renal, and systemic side effects were not significant. In advanced NSCLC the addition of alpha-2B interferon did not increase the cisplatin-induced response rate. Further studies should be performed to determine the real value of chemotherapy response in tumors showing positive immunoreactivity for neural markers such as NSE and Leu-7.

Adult

Sequential combination of methotrexate (MTX), 5-fluorouracil (FU), and high-dose folinic acid (FA) in advanced colorectal cancer: double biochemical modulation?

Thirty evaluable patients were treated with methotrexate (MTX) 200 mg/m2, i.v. infusion over 60 minutes, 24 hours prior to the administration of 5-fluorouracil 600 mg/m2, and folinic acid 200 mg/m2, i.v. infusion over 60 minutes, every 2 weeks. A partial or complete response was achieved in 12 patients (40%), and disease stable in 10 patients (33%). Median actuarial survival was 18 months. Side effects, which were within acceptable limits, included 11 cases of stomatitis (5 Grade 3), 3 cases of leukopenia (Grade 2) and 12 cases of mild nausea and vomiting. We conclude that the present combination is active in metastatic colorectal cancer with mild toxicity. These results are being confirmed and a randomized trial is being carried out to prove that this combination holds therapeutic advantage.

Adenocarcinoma

Randomized trial for the control of acute vomiting in cisplatin-treated patients: high-dose metoclopramide with dexamethasone and lorazepam as adjuncts versus high-dose alizapride plus dexamethasone and lorazepam. Study of the incidence of delayed emesis.

This study investigated the antiemetic activity of two different acute antiemesis regimens in patients receiving cisplatin-based chemotherapy. Seventy-four patients were treated with high-dose metoclopramide, dexamethasone and lorazepam (MDL) and 71 patients received high-dose alizapride, dexamethasone and lorazepam (ADL). Complete protection from vomiting was 50% in MDL-treated patients as compared with 30% in the ADL arm (p = 0.04). Incidence of delayed emesis was assessed in the first 82 patients accrued for the 120 h postcisplatin, being 69 and 60% in MDL and ADL, respectively.

Antiemetics

[The description of a new cellular type, Pinocchio cells, induced during the treatment of solid tumors with interleukin-2].

Three patients with renal adenocarcinoma and one with metastatic malignant melanoma were treated with continuous intravenous infusion of 18 x 10(6) IU/m2/day interleukin-2 during 5 days per week (2 weeks). Overall 60% of the calculated dose was administered owing to the development of severe toxicity. Among the hematological effects, eosinophilia was found in all patients, which was more marked 15-20 days after therapy was started. In addition, 15% of atypical lymphocytes were found in peripheral blood. These cells, denominated Pinocchio cells, show a cytoplasmatic prolongation with azurophilic granulation. Their cytochemical study disclosed a marked positivity for acid phosphatase and alpha-naphthyl acetate esterase, and a variable positivity for dipeptidyl-amino peptidase (DAP IV). The immunophenotype revealed that is a T lineage cell population, basically CD 3+, with small or absent positivity for the monoclonal CD 19 antibody. The presence of Pinocchio cells, which are effector cells mediating tumor destruction by an apoptosis mechanism, is related to the administered dose of interleukin-2.

Adenocarcinoma

A randomized study of two vindesine plus cisplatin-containing regimens with the addition of mitomycin C or ifosfamide in patients with advanced non-small cell lung cancer.

The current trial was carried out to assess the survival enhancement achieved, if any, by adding ifosfamide to vindesine and cisplatin (IVP) in contrast to mitomycin plus vindesine and cisplatin (MVP). Between June 1986 and September 1988, 110 patients were randomly allocated to receive either ifosfamide (3 g/m2 plus 3 g/m2 of mesna) or mitomycin 8 mg/m2, on days 1, 29, and 71 only. In both arms vindesine was given 3 mg/m2 weekly X 5 then every 2 weeks. In the MVP arm, 120 mg/m2 of cisplatin was administered on days 1 and 29 and then every 6 weeks, whereas in the IVP arm 100 mg/m2 of cisplatin was given on the same time schedule. One hundred three patients were evaluable for response and toxicity and 56% of patients had Mountain's Stage IV disease. The response rate was 26% (14/53 patients) in the MVP arm (95% confidence interval, 14%-39%) and 20% (ten of 50 patients) in the IVP arm (95% confidence interval, 10%-34%). Neither the response rate nor the median survival times were significantly different, although more nephrotoxicity was produced in the MVP arm, grade 1+ in 43% versus 26% in IVP arm (P = 0.04). Results obtained from this study fail to demonstrate that mitomycin or ifosfamide have a synergistic effect on the efficacy of the vindesine/cisplatin combination.

Adult

Cyclophosphamide and ifosfamide combination as neoadjuvant chemotherapy for locally advanced nonsmall-cell lung cancer: a meta-analytic review.

Twenty-three patients with marginally resectable and unresectable non-small-cell lung cancer (stages IIIA and IIIB) were treated by neoadjuvant chemotherapy. All patients received three cycles of preoperative chemotherapy with two alkylating agents, cyclophosphamide 2.5 g/m2 intravenously (i.v.) and ifosfamide 3.5 g/m2 i.v., mesna 12 g/m2 was given additionally to prevent drug hematuria. Six of 23 patients (26%) had partial response. Of the seven patients who underwent thoracotomy, two were completely resected, but with macroscopic residual disease. Mean time to progression for the whole group was 7 months. Fifteen patients had progression of disease, with local metastases only in six, and distant metastases in eight. After administering 52 chemotherapy cycles, cyclophosphamide-ifosfamide doses were cut down, as eight of 16 patients required hospitalization for fever during neutropenia nadirs. This two-alkylating (non-cisplatin) regimen, unlike cisplatin-based regimens, was ineffective, and further trials are not recommended.

Aged

[Spontaneous rupture of the spleen disclosing pheochromocytoma].

The authors report a case of spontaneous rupture of spleen inaugurating the symptomatology of a pheochromocytoma. After presenting the observation, clinical problems are considered with a deceptive abdominal symptomatology and myocardial ischemia that could be part of an "adrenergic myocarditis"; the mechanism of ruptured spleen is analyzed. The diagnosis approach is discussed through a reliability study of various explorations: computed tomography has a sensitivity ranging from 93 to 97% which approaches 100% when associated with magnetic resonance, methyl-iodo-benzyl-guanidine scanning seems to be provided with similar reliability. During checking up for pheochromocytoma spreading, ectopic location was not found, but a cold thyroid nodule was detected which allowed suspecting a SIPPLE syndrome. The three-stage surgical approach was required by symptomatology, hemostasis splenectomy, lateral pheochromocytoma excision after a short preparation by blocking alpha and beta, and then total thyroidectomy after extemporaneous confirmation of the existence of a medullary carcinoma of the thyroid. This pathologic association leading to a SIPPLE syndrome is listed as part of the multiple endocrine neoplasias of type II (MEN II).

Adrenal Gland Neoplasms