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Biomedical subjects

C Sessa

Publications and source records attributed to C Sessa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Management of symptomatic and asymptomatic popliteal venous aneurysms: a retrospective analysis of 25 patients and review of the literature.

OBJECTIVE: Popliteal venous aneurysms (PVAs) are an uncommon but potentially life-threatening disease because they can be a source for pulmonary emboli (PE). With the widespread use of venous duplex scanning, PVAs are increasingly found in patients with deep or superficial vein insufficiency, and questions have arisen as to the management of these aneurysms. The purpose of this study was to review our experience in the management of PVAs diagnosed in patients with PE and in patients with chronic venous diseases. METHODS: Twenty-five patients with PVAs were treated in two centers between 1985 and 1999. There were 20 women and five men, with an average age ranging from 33 to 79 years (mean age, 59 years). Twenty-four percent (6/25) presented with PE, and 76% (19/25) of PVAs were discovered during investigation for chronic venous disease (varicosities, n = 13; post-thrombotic symptoms, n = 6). The diagnosis of PVA was achieved in all cases with venous duplex scanning and phlebography. Aneurysms were located in the proximal popliteal vein (n = 17) and at the saphenopopliteal junction (n = 8). Seventy-two percent (18/25) of PVAs were saccular, and 40% (10/25) had an intraluminal thrombus. Two patients with PE underwent cardiac arrest, with one requiring a pulmonary embolectomy. The Fisher exact test showed a statistically significant correlation between PE and the presence of thrombus (50% vs 7% without thrombus, P =.02). Aneurysms were treated with tangential aneurysmectomy and lateral venorrhaphy (n = 19), resection with end-to-end anastomosis (n = 2), resection with interposition of the greater saphenous vein (n = 2) or the superficial femoral vein (n = 1), and resection with vein transposition (n = 1). Two patients who experienced a PE had an inferior vena cava filter placement before surgical repair of the PVA. RESULTS: Mean follow-up was 63 months (range, 11-168 months). No operative deaths occurred, and no patient had evidence of a recurrent PE. Postoperative minor complications (20%) included transient common peroneal nerve palsy (n = 2), postoperative hematoma (n = 2), and wound infection (n = 1). Postoperative thrombosis of the surgical repair occurred in three patients, and patency was restored with anticoagulation therapy. CONCLUSION: Despite its rarity, PVAs should be ruled out with venous duplex scanning in patients with PE and in patients presenting with chronic venous diseases. Because of the unpredictable risk of thromboembolic complications, surgical treatment that is accompanied by a low morbidity rate is indicated in all PVAs. Tangential aneurysmectomy with lateral venorrhaphy is the procedure of choice.

Adult↗
PubMed2000

Vasoconstrictor effects of iso-prostaglandin F2alpha type-III (8-iso-prostaglandin F2alpha) on human saphenous veins.

Free radical generation can initiate the peroxidation of arachidonic acid, resulting in a non-cyclooxygenase-dependent production of bioactive prostaglandin F2-like compounds. We have investigated the effects of iso-prostaglandin F2alpha type III, (iPF2alpha-III, formerly named 8-iso prostaglandin F2alpha) on human saphenous veins, and characterized the underlying mechanisms. In organ baths, the contractile effects of iPF2alpha-III were tested on saphenous vein rings coming from 22 patients. iPF2alpha-III induced concentration-dependent contractions of isolated human saphenous veins. The maximal contraction did not differ significantly from that of prostaglandin F2alpha (PGF2alpha). The pD2 values for iPF2alpha-III, PGF2alpha, endothelin-1 (ET-1), and U46619 (a stable thromboxane A2 mimetic) were 6.31+/-0.12, 5.66+/-0.13, 7.37+/-0.08, and 7.99+/-0.31, respectively (p < 0.001 for U46619 vs. iPF2alpha-III and PGF2alpha; and ET-1 vs. PGF2alpha). Emax values of iPF2alpha-III, PGF2alpha, ET-1, and U46619 were 137.7+/-24.3%, 145.9+/-7.5%, 92.9+/-16.8%, and 238.7+/-23.7%, respectively (p < 0.001 for U46619 vs. iPF2alpha-III, PGF2alpha and ET-1; and for PGF2alpha vs. ET-1). The responses to iPF2alpha-III were inhibited by GR 32191 10(-7) M, a TP-receptor antagonist, without affecting the maximal response (pD2 values were 5.98+/-0.06 in the absence, and 5.22+/-0.05 in the presence of GR32191; p < 0.001). Concentration-effect curves to iPF2alpha-III were not affected by phosphoramidon 10(-5) M (an endothelin converting enzyme inhibitor), BQ123 10(-6) M (a selective ET(A)-receptor antagonist), BQ788 10(-6) M (a selective ET(B)-receptor antagonist), and indomethacin 10(-5) M (a cyclooxygenase inhibitor). Finally, the contractile response of iPF2alpha-III did not involve the release of thromboxane B2 and ET-1, measured using enzyme immunoassays. This study demonstrates that iPF2alpha-III is a vasoconstrictor of human saphenous veins, with a potency fourfold greater than that of PGF2alpha, and 50 times less than that of the thromboxane A2 mimetic, U46619. These effects are mediated at least in part by TP-receptor stimulation, but do not involve thromboxane A2 or ET-1 release.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Cyclosporine A and cremophor EL induce contractions of human saphenous vein: involvement of thromboxane A2 receptor-dependent pathway.

Chronic treatment with Sandimmune (cyclosporine A [CsA] dissolved in Cremophor EL [CrEL]) is often associated with hypertension and nephrotoxicity. The aims of the present study were to assess the effect of Sandimmune and its two main components (CsA and CrEL) on human saphenous veins and to study the underlying mechanism of their contractile responses. In organ bath, concentration-response curves for Sandimmune (36 ng/ml-120 microg/ml of CsA). CsA (36 ng/ml-120 microg/ml), or CrEL (2.4 microg/ml-8 mg/ml) were elicited in the presence of a thromboxane A2 (TXA2) receptor antagonist (GR32191, 0.3 microM), a cyclooxygenase inhibitor (indomethacin, 1 microM), a 5-lipoxygenase inhibitor (AA861, 10 microM), or their respective vehicles. In addition, the production of TXA2 after CsA challenge was assessed by enzyme immunoassay. Sandimmune, CsA, and CrEL induced concentration-dependent contractions on human saphenous veins. In terms of potency, CsA was a more potent vasoconstrictor agent than CrEL (EC50 values: 11.9+/-3.7 microg/ml (CsA, n = 12) vs. 1.2+/-0.4 mg/ml (CrEL, n = 16), p < 0.05). In contrast, in terms of efficacy, CrEL induced greater contractions than CsA (Emax (% of KCl 90 mM-induced contraction): 98.1+/-16.1% (CrEL, n = 16) vs. 17.0+/-4.3% (CsA, n = 12) p < 0.05). Pretreatment with GR32191 significantly reduced by 85% and 56% the contractions elicited by CsA and CrEL, respectively, whereas indomethacin had no effect. Finally, CsA (12 and 120 microg/ml) failed to stimulate TXA2 production. These in vitro data suggest that Sandimmune-induced contractions on human vascular smooth muscle appear to be mediated by CsA in the therapeutic ranges of doses and by both CsA and CrEL, which, in supratherapeutic doses, acted through a TXA2 receptor-dependent pathway.

Biphenyl Compounds↗
PubMed2000

Role of duplex imaging in endovenous obliteration for primary venous insufficiency.

PURPOSE: To assess the role of duplex imaging in defining suitable pathological anatomy for endovenous obliteration and characterizing its treatment outcomes over time. METHODS: Eighteen lower limbs in 17 patients (12 women; mean age 48 years; range 29-74 years) presenting with varicose greater saphenous veins (GSVs) were treated with endovenous obliteration without adjunctive high ligation. Duplex imaging was used as an intraprocedural guidance tool for vein access and catheter positioning and for preprocedural evaluation and serial surveillance after the procedures. RESULTS: In the 18 limbs, preprocedural duplex scanning defined reflux owing to incompetence of the terminal valve (n = 6), subterminal valve (n = 9), or truncal valve (n = 3). Duplex imaging facilitated percutaneous vein puncture and was essential in catheter positioning at the saphenofemoral junction (SFJ). At 1 week, the saphenous trunks of all 18 limbs were either shrunken and obliterated (n = 7) or occluded by thrombus without shrinkage (n = 11). By 6 months, 7 GSVs were no longer sonographically visible, 10 were shrunken and obliterated, and 1 had a segmental partial recanalization. In the 15 limbs with terminal or subterminal valve incompetence at 1 week, 5 had total SFJ obliteration, 4 had > or =1 patent tributaries draining directly into the femoral vein through an open SFJ, and 6 had > or =1 patent tributaries draining into an open SFJ through a short (<2 cm) proximal saphenous trunk. By 6 months, only 1 limb had total SFJ occlusion; the other 14 had at least 1 persistent or reopened tributary. CONCLUSIONS: Duplex scanning is indispensable for selecting patients, guiding the procedure, and defining the morphological maturation and hemodynamic changes that appear to characterize successful endovenous obliteration.

Adult↗
PubMed2000

Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer.

PURPOSE: To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. RESULTS: A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P: <.01) and less peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia (P: <.01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Phase I clinical and pharmacological study of oral methoxymorpholinyl doxorubicin (PNU 152243).

PURPOSE: The methoxymorpholinyl doxorubicin analogue PNU 152243 was brought into clinical studies because of preclinical observations of its non-cross-resistance in mdr tumor cells, dose-limiting neutropenia, lack of cardiotoxicity, and antitumor activity after oral administration. METHODS: PNU 152243 was given orally every 4 weeks to 21 adults with a variety of solid tumors at doses ranging from 59 to 940 microg/m(2). Antiemetic prophylaxis with 5-HT3 antagonists and steroids, given i.v. on day 1 and orally on days 2-8, was required beginning with the dose of 118 microg/m(2). The plasma pharmacokinetics of PNU 152243 were determined by an HPLC method with fluorescence detection. The in vitro myelotoxic effects on granulocyte macrophage-colony forming cells (GM-CFC) of the plasma from 11 patients, obtained 4 and 6 h after treatment at all dose levels, were also assessed. RESULTS: Neutropenia was the main hematologic toxic effect and the maximum tolerated dose (MTD) for myelotoxicity was 940 microg/m(2), with neutropenia grade 3-4 in two of three patients. Dose-dependent nausea and vomiting were dose-limiting and the MTD for gastrointestinal toxicity was fixed at 820 microg/m(2), with grade 4 vomiting in one of two patients. Other frequent toxic effects were diarrhea and fatigue. Peak levels of PNU 152243 were achieved 4 h after dosing. Dose-dependent Cmax and AUCExp, and significant interpatient variability of the main pharmacokinetic parameters were found. Very low levels of the 13-dihydrometabolite PNU 155051 were detected only at the highest doses. The hematotoxicity tests showed a <70% colony growth inhibition with no correlation between the growth inhibition effect and the degree of myelotoxicity in the same patient. Plasma concentrations of PNU 152243 were 1000 times lower than the concentration inhibiting the growth of 70% of colonies. No objective tumor responses were seen. CONCLUSIONS: Owing to the occurrence of severe and prolonged nausea and vomiting, the clinical development of oral PNU 152243 was discontinued. The higher-than-expected neutropenia and its lack of relationship with plasma levels of PNU 152243 and its 13-dihydroderivative PNU 155051 might be related to the formation of potent cytotoxic metabolites present in human plasma at undetectable concentrations and with prolonged half-life, as suggested by hematotoxicity tests performed with plasma from patients in GM-CFC assays.

Administration, Oral↗
PubMed1999

Differential toxicity of anticancer drugs on late (GM-CFC) and early (LTC-IC) hemopoietic progenitors in vitro.

The clinical hematological toxicity of cytotoxic drugs can be acute, with a nadir of neutrophil count after 2 weeks and recovery the following week, or subacute, with a nadir of neutrophil count after 3 weeks and recovery in the following 2-3 weeks. The explanation usually given for this difference is that drugs in the first group are more toxic to mature hemopoietic precursors, while drugs of the second type are more toxic to undifferentiated cells. In an attempt to verify this hypothesis, we compared in vitro the effect of toxic doses of etoposide and tallimustine as representatives of drugs with acute toxicity, and of BCNU, melphalan, and carzelesin as representatives of drugs with subacute toxicity. Their effects were studied separately on more differentiated and earlier progenitors represented by granulocyte-macrophage colony-forming cells (GM-CFC) and long-term culture-initiating cells (LTC-IC), respectively. Etoposide, melphalan, BCNU, and carzelesin showed higher toxicity in differentiated than in early precursors: the concentration of drug inhibiting 70% (ID70) of GM-CFC inhibited only by 10-40% the growth of LTC-IC. Tallimustine, in contrast, inhibited both GM-CFC and LTC-IC at comparable levels. These results do not correspond to the clinical pattern of myelotoxicity observed for those drugs. We conclude that the differential effects of antitumor drugs on later (GM-CFC) or earlier (LTC-IC) hemopoietic precursors may not represent a valid model for the pattern of myelotoxicity observed in humans.

Animals↗
PubMed1999

Pharmacokinetic interactions of paclitaxel, docetaxel and their vehicles with doxorubicin.

BACKGROUND: The combination of doxorubicin (Dx) with paclitaxel or docetaxel is clinically effective but there are concerns regarding the higher incidence of cardiotoxicity of the combination compared with Dx alone. The mechanism of the increased toxicity is still unclear. PURPOSE: To assess whether there is a pharmacokinetic interaction between paclitaxel, docetaxel or their vehicles and Dx in mice. MATERIALS AND METHODS: CDF1 male mice were treated with Dx either alone (10 mg/kg i.v.) or in combination with paclitaxel (25 mg/kg) or docetaxel (25 mg/kg) or their vehicles, i.e., cremophor-ethanol-glucose (cremophor) or polysorbate80-ethanol-glucose (polysorbate). Four mice were killed 4, 8 or 24 hours after Dx in each experimental group and Dx was assayed in serum and in heart, liver, kidney and spleen by HPLC. RESULTS: Four hours after treatment the concentrations of Dx in heart, liver and kidney were much higher in mice concomitantly treated with paclitaxel, docetaxel (dissolved in either cremophor or polysorbate) and cremophor. At subsequent times the differences were modest and only reached statistical significance in a few cases. Dx metabolites were modified by concomitant treatment with taxanes or their vehicles. In particular, the levels of Dx aglycone in liver and kidney were significantly lower in mice treated with the combination than in mice given Dx alone. CONCLUSIONS: Paclitaxel, docetaxel and cremophor when given together with Dx modify its distribution and metabolism, increasing Dx levels in many tissues including the heart. This might have some bearing on the toxicity of regimens in which Dx is combined with taxanes.

Animals↗
PubMed1999

Oxaliplatin in ovarian cancer.

Oxaliplatin [trans-1-diaminocyclohexane (DACH) platinum, L-OHP] was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumour activity observed in experimental models resistant to cisplatin. The antitumour activity so far observed in phase II studies, in which L-OHP was mainly given at the dose of 130 mg/m2 as 2-hour infusion, ranged between 15% and 30% and has confirmed the preclinical data. These results strongly support the need for additional studies in patients with tumour primarily resistant to cisplatin to establish a role of L-OHP. Neurotoxicity, in the form of a peculiar sensory neuropathy, is the most important side effect, because it is cumulative after repeated administration of the single agent or of combinations with other highly active but neurotoxic antitumour drugs like taxanes and other platinum analogues. Further clinical development of L-OHP needs to take into account the characteristics of other available active drugs and the distinctive preclinical and clinical features of this DACH platinum complex.

Antineoplastic Agents↗
PubMed1999

Advanced epithelial ovarian cancer: 1998 consensus statements.

BACKGROUND: During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for research of advanced epithelial ovarian cancer. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting. RESULTS: One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Gemcitabine in the treatment of ovarian cancer.

Gemcitabine is a new nucleoside antimetabolite with established activity against solid tumours. In previously treated patients the response rate with the drug alone was around 13%. Combination therapy with gemcitabine-cisplatin or gemcitabine-paclitaxel induced responses in 53 and 40% respectively. In previously untreated patients with poor prognostic features a 24% response rate was reported for the drug alone, but in combination with cisplatin remissions were found in 53%-71% of patients. Gemcitabine, paclitaxel, and carboplatin (or cisplatin) in combination appeared to be a feasible and active combination. In a pilot with eight previously treated patients all obtained a remission and in untreated patients a remission occurred in all evaluable patients either clinically or measured by a decrease of CA 125. Dose-limiting toxicity is mainly haematological.

Antimetabolites, Antineoplastic↗
PubMed1999

Saturable metabolism of continuous high-dose ifosfamide with mesna and GM-CSF: a pharmacokinetic study in advanced sarcoma patients. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: The aim of this study was to assess the pharmacology, toxicity and activity of high-dose ifosfamide mesna +/- GM-CSF administered by a five-day continuous infusion at a total ifosfamide dose of 12-18 g/m2 in adult patients with advanced sarcomas. PATIENTS AND METHODS: Between January 1991 and October 1992 32 patients with advanced or metastatic sarcoma were entered the study. Twenty-seven patients were pretreated including twenty-three with prior ifosfamide at less than 8 g/m2 total dose/cycle. In 25 patients (27 cycles) extensive pharmacokinetic analyses were performed. RESULTS: The area under the plasma concentration-time curve (AUC) for ifosfamide increased linearly with dose while the AUC's of the metabolites measured in plasma by thin-layer chromatography did not increase with dose, particularly that of the active metabolite isophosphoramide mustard. Furthermore the AUC of the inactive carboxymetabolite did not increase with dose. Interpatient variability of pharmacokinetic parameters was high. Dose-limiting toxicity was myelosuppression at 18 g/m2 total dose with grade 4 neutropenia in five of six patients and grade 4 thrombocytopenia in four of six patients. Therefore the maximum tolerated dose was considered to be 18 g/m2 total dose. There was one CR and eleven PR in twenty-nine evaluable patients (overall response rate 41%). CONCLUSION: Both the activation and inactivation pathways of ifosfamide are non-linear and saturable at high-doses although the pharmacokinetics of the parent drug itself are dose linear. Ifosfamide doses greater than 14-16 g/m2 per cycle appear to result in a relative decrease of the active metabolite isophosphoramide mustard. These data suggest a dose-dependent saturation or even inhibition of ifosfamide metabolism by increasing high dose ifosfamide and suggest the need for further metabolic studies.

Adult↗
PubMed1999

Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer.

BACKGROUND: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile. PATIENTS AND METHODS: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with > or = 2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography. RESULTS: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) < 0.1 x 10(9)/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2 and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 x 10(9)/l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotoxicity. Antitumor activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30+), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months. CONCLUSIONS: The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimens.

Adult↗
PubMed1999

Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer.

A significant myeloprotective effect of melatonin in mice treated with etoposide, cyclophosphamide or carboplatin has been reported. The present study was designed to evaluate if the same effect could be observed in patients receiving chemotherapy. Twenty previously untreated patients with inoperable lung cancer received two cycles of carboplatin (given at area under the curve 5 by the Calvert formula) on day 1 and etoposide (150 mg m(-2) i.v.) on days 1-3 every 4 weeks. Melatonin 40 mg or placebo (double-blind) was given orally in the evening for 21 consecutive days, starting 2 days before chemotherapy. Patients were randomized to receive melatonin either with the first or the second cycle. Complete blood cell count with differential was done three times per week for 3 weeks. The median age of the cohort was 60 years (range 42-69), 16 patients had non-small cell and four patients small-cell lung cancer, 12 stage III and eight stage IV disease. In a multivariate analysis including age, sex, diagnosis, stage, performance status, doses of carboplatin and etoposide, and concomitant treatment with melatonin or placebo, the haematological parameters--depth and duration of toxicity for haemoglobin, platelets and neutrophils (ANC)--were not significantly different between cycles with/without melatonin. The mean ANC nadir and the mean number of days with ANC < 0.5 x 10(9) l(-1) were 0.5 x 10(9) l(-1) and 2.5 days, respectively, with/without melatonin. We concluded that, in patients with lung cancer, melatonin given orally at a dose of 40 mg per day for 21 days in the evening, does not protect against the myelotoxic effect of carboplatin and etoposide.

Adult↗
PubMed1999

Vascular surgical society of great britain and ireland: mid-term results of arterial allograft below-knee bypasses for limb salvage

BACKGROUND: Arterial allografts (AAs) have been recently reconsidered in the treatment of critical limb ischaemia when vein material is absent, because of the disappointing results with artificial grafts. The aim of this study was to report the results observed in three centres where AAs were used for infrainguinal reconstruction in critical limb ischaemia. METHODS: Between 1991 and 1997, 165 AA bypasses were performed in 148 patients (90 men) with a mean age of 70 (range 20-93) years. Indications for operation were rest pain in 54 patients and tissue loss in 111. Mean resting ankle pressure was 53 mmHg in 96 non-diabetic patients and mean transcutaneous partial pressure of oxygen was 10 mmHg in 52 diabetic patients. AAs were obtained from cadaveric donors. The distal anastomosis was to the below-knee popliteal artery in 34 cases, to a tibial artery in 114 and to a pedal artery in 17. RESULTS: At 30 days, the mortality rate was 3 per cent, primary patency 83 per cent, secondary patency 90 per cent and limb salvage rate 98 per cent. During follow-up (mean 31 months) 65 grafts failed primarily. Causes of primary failure were thought to be progression of the distal disease in 15 cases, myointimal hyperplasia in 16, graft degradation in ten (four dilatations, three stenoses, two ruptures and one dissection), other causes in eight and not known in 16. Primary and secondary patency rates at 3 years were 35(s.e. 9) per cent and 42(s. e. 10) per cent. The limb salvage rate at 3 years was 76(s.e. 8) per cent. CONCLUSION: AAs lead to a good foot salvage rate but poor patency rates. The results are similar to those obtained with polytetrafluoroethylene grafts.

Journal Article↗
PubMed1999

Antagonistic effects of losartan on thromboxane A2-receptors in human isolated gastroepiploic artery and saphenous vein.

In addition to its AT1-receptor antagonist activity, losartan has been shown to antagonize thromboxane A2 (TXA2)-induced contraction of animal vessels. We investigated for the first time in human isolated gastroepiploic artery (GEA) and saphenous vein (SV) the TXA2/PGH2-receptor antagonist activity of losartan in the presence of indomethacin (1 microM) and N(omega)-nitro-L-arginine (100 microg). Losartan at concentrations of > or =1 microM on GEA and from 10 microM on SV significantly shifted U46619-induced contractions to the right. In addition, 100 microM losartan decreased by 34% the amplitude of the contraction to U46619 on both GEA and SV. The potency of losartan for the TXA2 receptor was 50- and 80-fold lower than that for the AT1 receptor on human GEA and SV, respectively. This inhibitory effect of losartan appeared selective for angiotensin II and TXA2-induced contractions because 100 microM losartan did not modify either endothelin-1- or KCl-induced contraction in human SV, although a reduction of norepinephrine- and 5-hydroxytryptamine-induced contraction was observed in human GEA and SV, respectively. In conclusion, losartan is an antagonist of TXA2 receptor on human GEA and SV. However, this antagonist activity occurred for a relative high dose of losartan, suggesting that it contributes at a low level, if any, to its antihypertensive effect.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗