Rio de La Plata study: a multicenter, cross-sectional study on cardiovascular risk factors and heart failure prevalence in peritoneal dialysis patients in Argentina and Uruguay.

A multicenter cross-sectional study was performed to evaluate the prevalence of heart failure (HF) and the associated cardiovascular (CV) risk factors in 298 peritoneal dialysis (PD) patients from Argentina and Uruguay, representing almost 30% of the total number of PD patients in the two countries. Bidimensional echocardiography, electrocardiography, and biochemical analysis were performed. Systolic HF was defined as an ejection fraction <50%. According to echocardiography, 84.6% showed left ventricular hypertrophy (LVH), 38.3% valvular heart disease, and 35.4% valvular calcification, whereas 20% showed intraventricular conduction disturbances on the electrocardiogram. The prevalence of CV risk factors was of 73% hypertension, 51% sedentarism, 18% diabetes, 16.8% obesity, 12% smokers, 42.3% phosphorus >5.5 mg per 100 ml, 42.3% parathyroid hormone>300 pg ml(-1), and 29.6% calcium phosphate product >55. The prevalence of systolic HF was 9.9%, being significantly associated with diabetes: odds ratio (OR)=4.11 (P<0.006) and hypoalbuminemia: OR=3.45 (P<0.011). Forty percent of patients with a diagnosis of left ventricular dysfunction at the time of the study were asymptomatic. Variables associated with LVH in the multivariate analysis were anemia (OR=4.06; P<0.001) and previous hemodialysis (OR=1.99; P<0.031). The identification of reversible risk factors associated to HF and the diagnosis of asymptomatic ventricular dysfunction in this PD population will lead our efforts to establish guidelines for prevention and early treatment of congestive HF in patients on PD.

Oesophageal cavernous haemangioma.

Esophageal cavernous haemangioma is an uncommon benign neoplasm. These tumors are usually discovered incidentally as they are often asymptomatic. The symptoms, if present, are bleeding and dysphagia. Endoscopic and radiographic features are nonspecific and histopathologic examination is required for definitive diagnosis and appropriate treatment. We herein report a case of a 69-year old man who presented with complain of mild dysphagia for solid foods. Endoscopic evaluation with transesophageal ultrasonography and CT revealed a 5 cm intramural tumor in the posterior wall of the upper esophagus. The tumor was resected and histological examination showed an esophageal cavernous haemangioma.

Nimesulide as a downregulator of the activity of the neutrophil myeloperoxidase pathway. Focus on the histoprotective potential of the drug during inflammatory processes.

Neutrophils, recruited to tissue sites of inflammation, release a variety of oxidants and enzymes, which are responsible for tissue damage. Among the oxidants released are potent chlorinated compounds, such as hypochlorous acid and chloramines, which induce tissue cell damage and inactivate protease inhibitors, particularly alpha 1-antitrypsin, the specific inhibitor of neutrophil elastase. In studying a rational approach to the pharmacological control of neutrophil-mediated tissue injury, we investigated the activity of the anti-inflammatory drug nimesulide. This agent reduced the function of the myeloperoxidase pathway (which generates hypochlorous acid), by exerting a cell-directed inhibitory activity, as shown by measurement of superoxide anion and hydrogen peroxide production. Nimesulide also inactivated hypochlorous acid directly and protected alpha 1-antitrypsin from the neutrophil-mediated oxidation. Thus, neutrophil elastolytic activity may be attenuated by nimesulide-spared alpha 1-antitrypsin. The prevention of oxidative inactivation of alpha 1-antitrypsin by nimesulide strictly correlates with the drug's ability to suppress the extracellular availability of hypochlorous acid. Taken together, these data suggest that nimesulide may prevent tissue injury at sites of inflammation by maintaining natural host protective systems.

Cytoprotection against neutrophil-delivered oxidant attack by antibiotics.

In the present study we have investigated the effect of six antibiotics (penicillin G, ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) on the neutrophil cytolytic activity by using a system constituted of phorbol-12-myristate-13-acetate-triggered neutrophils and 51Cr-labelled lymphoblastoid Daudi target cells. The results demonstrate that five of these drugs (ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) are capable of inhibiting the neutrophil cytolytic activity by inactivating the hypochlorous acid (HOCl) generated extracellularly by the myeloperoxidase pathway and crucial to the target cell lysis. Penicillin G had no effect on neutrophil-mediated cytolysis. Thus, these data demonstrate that ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin lower the neutrophil-mediated target cell damage by a HOCl-scavenging mechanism, suggesting a possible cytoprotective role for these drugs during infections.

Phase II study of tamoxifen and high-dose retinyl acetate in patients with advanced breast cancer.

Retinoids have shown a tumor growth inhibition and a synergistic activity with hormonal manipulations in human breast cancer cell lines and rat mammary carcinoma. To investigate the potential usefulness of this synergistic activity in human breast cancer, 33 postmenopausal patients with advanced disease were treated with the combination of tamoxifen (10 mg p.o. three times a day) and retinyl acetate (300,000 IU p.o. daily). Out of 31 evaluable patients, 3 achieved complete response, 9 partial response (overall response rate: 38.5%, 95% confidence interval = 21%-56%) and 16 (52%) showed no change. The median duration of response was 11.5 months (range: 3-19+ months), while the 2-year overall survival rate for the entire group of patients was 63%. Toxicity was generally mild, hot flushes, nausea (and/or vomiting), headache and cutaneous itching being the most frequent side-effects. Only 1 patient discontinued treatment for severe toxicity. These preliminary results suggest that the combination of tamoxifen and high-dose retinyl acetate is a safe and effective regimen for breast cancer patients. However, the study design does not allow us to establish whether the very low rate of early disease progression we observed might be related to a possible synergistic effect between retinoids and antiestrogens or rather to the quite indolent disease of the patients who have been selected for entry into this trial.

Identification of fast and slow growing rhizobia nodulating soybean (Glycine max [L.] Merr) by a multiplex PCR reaction.

Two DNA fragments, a 730-bp and a 900-bp fragment, one homologous to host cultivar specificity genes nolBT of Sinorhizobium fredii and the other one homologous to RSalpha, an insertion-like sequence present in Bradyrhizobium japonicum, were generated by polymerase chain reaction (PCR) with two pairs of primers. The amount of each fragment generated by the multiplex PCR was proportional to the amount of template DNA present. The amplification of the 900-bp RSalpha fragment was more sensitive, since it was amplified from a smaller amount of template DNA than the 730-bp nolBT fragment. By running the multiplex reaction in the presence of template DNA isolated from different sources, we confirmed that the reaction can discriminate between S. fredii, Bradyrhizobium japonicum and Sinorhizobium xinjiangensis.

Interleukin-8 down-regulates the oxidative burst induced by tumor necrosis factor alpha in neutrophils adherent to fibronectin.

Human neutrophils (5 x 10(4) incubated on fibronectin precoated wells released 2.83 +/- .25 nmoles of superoxide (0(2)-) (x +/- 1 SEM, n = 15) in response to 5.9 nM (100 ng/ml) Tumor Necrosis Factor Alpha (TNF). On the contrary, the 0(2)- production induced by interleukin-8 (IL-8) (doses ranging from 0.1 nM to 1 microM) was comparable to that of "resting" cells (< .6 nmoles/5 x 10(4) cells). IL-8 (100 nM) did not affect the TNF-dependent 0(2)- production when added with TNF at the beginning of the assay, but reduced it by approximately 80% when added with TNF on neutrophils previously incubated for 1 hour on fibronectin. As compared with IL-8, N-formyl-methionyl-leucyl-phenylalanine (FMLP, 100 nM) failed to suppress the TNF-triggering of the oxidative burst in neutrophils plated on fibronectin. The data suggest that the interaction of neutrophils with fibronectin uncovers the capacity of IL-8 to limit the cell response to TNF, without affecting the response to the combination of FMLP and TNF. Thus, although the chemotactic factors IL-8 and FMLP share the capacity of triggering the oxidative burst of neutrophils incubated in suspension, only IL-8 has the potential to down-regulate the responsiveness of fibronectin-adherent cells to TNF.

Evaluation of the effects induced by four opiate drugs, with different affinities to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and on cortisol secretion in normal men.

In order to ascertain the subtype(s) of opioid receptors involved in the control of pituitary function the effects of four different opiate drugs (morphine, pentazocine, nalorphine and buprenorphine) were studied in four groups of six normal male volunteers. Each of the drugs tested induced, with varying degrees, both a significant increase in PRL and a significant decrease in LH and cortisol. On the contrary TSH secretion was stimulated by buprenorphine and morphine only and GH by nalorphine only. FSH did not change significantly after administration of any drug. Taking into account the different affinities of the drugs used by us for the different opioid receptors, our data do not allow to demonstrate a well-defined correlation between subtypes of opioid receptors and the control of pituitary hormone secretion. The possible explanations of this fact are discussed.

Genotoxicity testing of chloramphenicol in rodent and human cells.

The results of this work, carried out to extend the limited information at present available on the genotoxic potential of chloramphenicol (CAP), indicate that in millimolar concentrations this antibacterial agent produced a minimal amount of DNA fragmentation in both V79 cells and metabolically competent rat hepatocytes. Moreover, a level of DNA-repair synthesis indicative of a weak but positive response was detected in primary cultures of liver cells obtained from 2 of 3 human donors, and a borderline degree of repair was present in those prepared from rats. The promutagenic character of CAP-induced DNA lesions was confirmed by a low but significant increase in the frequency of 6-thioguanine-resistant clones of V79 cells, which, however, was absent when the exposure was done in the presence of co-cultured rat hepatocytes. Finally, oral administration to rats of 1/2 LD50 CAP did not increase the incidence of either micronucleated polychromatic erythrocytes or micronucleated hepatocytes. Taken as a whole these findings suggest that CAP should be considered a compound intrinsically capable of producing a very weak genotoxic effect, but only at concentrations about 25 times higher than those occurring in patients treated with maximal therapeutic dosages.

Ibuprofen inhibits adhesion-dependent neutrophil response by a glycoprotein-unrelated mechanism.

The anti-inflammatory drug ibuprofen was found to inhibit neutrophil aggregation and chemotaxis, triggered by the chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP). The drug did not modify the surface expression of the glycoprotein CD11b-CD18, required for both aggregation and chemotaxis. Consistent with this finding, ibuprofen did not affect the release of lactoferrin from secondary granules which contain CD11b-CD18 molecules in their membranes. As the drug failed to interfere with the neutrophil oxidant production and primary granule release, the results suggest that it acts primarily at the initial steps of the neutrophil response during inflammation, i.e. the cell recruitment at inflamed tissue sites. Moreover, the data prove that adhesion-dependent neutrophil responses required cell processes independent of CD11b-CD18 but controlled, at least in part, by ibuprofen-inhibitable pathways.

Multiparametric evaluation of functional outcome after pylorus-preserving duodenopancreatectomy.

The aim of the present study was to evaluate the clinical, morphological and functional results obtained in a group of patients previously submitted to Traverso-Longmire pylorus-preserving duodeno-pancreatectomy (PPDP). The study was performed as a clinical, endoscopic, radioisotopic and electro-manometric evaluation. An analysis of the results allowed us to conclude that: 1) most patients show good clinical features, and this becomes more evident as post-operative time progresses; 2) bile reflux gastritis is an infrequent event; 3) gastric emptying times in patients overlap those seen in control subjects, and progressive normalization occurs postoperatively. The best clinical results coexist with normal gastric emptying times; 4) gastrojejunal interdigestive motor activity shows a reduction in phase 3 and a relative increase in phase 2. We argue that the motor activity of the upper gastrointestinal tract can restore, from a functional point of view, the new anatomical situation. On the basis of the good clinical and functional results, pyloric preservation seems to be the most physiological procedure for the restoration of alimentary continuity following duodenopancreatic resection.

Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial.

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16 taking buprenorphine (26%). There were six drop-outs in the first group (9%) and seven in the second (11%). Serious symptoms arose more frequently in the buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were noted.

Combination of epirubicin and lonidamine for treatment of advanced breast cancer.

AIMS AND BACKGROUND: In vitro and in vivo studies have shown that lonidamine potentiates the cytotoxic effect of anthracyclines in simultaneous and sequential combination. On the basis of such evidence, we evaluated the activity and toxicity of a combination of epirubicin plus lonidamine in advanced breast cancer. METHODS: Between January 1991 and November 1993, 33 patients with advanced breast cancer, age < 75 years and PS < 2, were treated with epirubicin (75 mg/m2 i.v. on day 1, every 3 weeks), plus lonidamine (450 mg/day orally from day 1 continuously until disease progression). RESULTS: Thirty patients were evaluable for response: 4 achieved complete response (13%) and 8 partial response (27%) (total response rate = 40%), 6 (20%) had stabilization of disease, and 12 (40%) progression of disease. The median duration of response was 10 months (range, 4-24+ months). This scheme was tolerated, with a mild additional toxicity related to lonidamine: only WHO grade III myalgia in 1 patient (3%) and epigastralgia in 3 patients (9%). CONCLUSIONS: Although some patients seem to have benefited from the combination at the dose levels of the drug used in the study, the therapeutic advantages of addition of lonidamine remain unclear.

A randomized trial of chemotherapy with or without estrogenic recruitment in locally advanced breast cancer. North-West Oncology Group (GONO) Study, Italy.

The present phase III trial was carried out to verify whether a kinetic recruitment induced by low doses of diethylstilbestrol (DES) could increase the killing efficacy of chemotherapy in patients with locally advanced breast cancer. One-hundred and seventeen untreated patients with locally advanced breast cancer (stage IIIA/IIIB) were randomized to receive 3 courses of primary chemotherapy consisting of cyclophosphamide (600 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.) and fluorouracil (600 mg/m2 i.v.) (CAF) on day 1, or DES-CAF (DES, 1 mg orally days 1-3, CAF on day 4). The courses were repeated every 3 weeks. The patients who achieved an objective response were submitted to mastectomy followed by 3 courses of CAF alternated with 3 courses of CMF (cyclophosphamide, 600 mg/m2 i.v.; methotrexate, 40 mg/m2 i.v.; fluorouracil, 600 mg/m2 i.v.), with or without DES. The two treatment arms were well balanced in terms of clinical and pathologic features. There was no significant difference in response rates to induction chemotherapy between the two treatment arms (objective response rate, 63.3% for CAF and 56.1% for DES-CAF). Median overall survival was 49 and 47 months and median progression-free survival was 24 and 21 months for CAF and DES-CAF patients, respectively. Toxicity was not significantly different in the two groups, with the exception of leukopenia: DES chemotherapy was significantly more myelotoxic than the standard treatment, which resulted in a significant reduction in the actual dose intensity. In spite of the attractive experimental evidence, we conclude that so far there is no clinical advantage in the combination of estrogen and chemotherapy. Further research is needed to investigate different schedules of chemotherapy and hormones, or to test the possibility of combining various mitogens.

[The value of therapeutic needle aspiration in Reclus' disease]. / Valore dell'agoaspirato terapeutico nella malattia di Reclus.

308 mammary needle aspirations for suspected clinical forms of mammary cystitis were performed between 1971 and 1980 at the Savona Oncological Centre. The evacuated cystic cavity was always treated with a concentrated Lugol solution, the sclerosing and modifying properties of which foster wall adherence and prevent relapses. Non relapses were observed at 2 years' distance in the 194 patients checked. Relapses were observed in 11 patients only and in 20 cases the cytological examination was positive, revealing atypical cells. It is felt that this technique, which poses no risk to the patient could be a valid routine treatment for mammary cyst.

[Immunochemotherapeutic treatment of gastrointestinal neoplasms]. / Trattamento immunopolichemioterapico delle neoplasie gastrointestinali.

The results obtained with a three-fold association of drugs (VCR, 5Fu, MeCCNU) in the treatment of 68 patients suffering from advanced carcinoma of the gastroenteric system followed up over an approximately four year period at the Savona Oncology Centre are reported. The percentage of positive responses (CR + PR) was 75% for carcinoma of the colon-rectum and 44.4% for stomach cancer. The results obtained in intestinal carcinoma proved more satisfactory than those reported in the literature. This could be attributed to the contemporaneous use of Corynebacterium parvum which boosts the immunitary state and so enhances the defences of the host organism, making it more sensitive to polychemotherapy. In the light of this hypothesis, stress is laid on the need to use an immunochemotherapy approach for the treatment of advanced carcinoma of the gastroenteric apparatus.

[Comparison of 2 protocols of polychemotherapy in the treatment of invasive carcinoma of the breast]. / Raffronto comparativo tra due protocolli polichemioterapici nel trattamento del carcinoma invasivo della mammella.

Two protocols, namely VAME (VCR, ADR, MTX, DEDX) and CMF (CTX, MTX, 5 FU), were used in the treatment of 77 menopausal patients with invasive breast cancer at the Savona Oncological Hospital between December 1976 and November 1980. CR + PR was obtained in 81.25% of those treated with VAME (group 1) and 55.18% of those treated with CMF (group B). The median and overall percentage of survival was higher in group A, and the free interval was longer, especially in patients with PR. This protocol also caused fewer subjective and objective disturbances and is thus regarded as more satisfactory, particularly since the main aim of antiblastic management is to improve and length and the quality of life.

[Use of calcitonin in neoplastic osteolysis]. / Impiego della calcitonina nelle osteolisi neoplastiche.

Forty patients with various neoplasias and radiological and scintigraphic evidence of multiple osteolytic lesions were studied between March 1979 and December 1981 at the Savona Oncology Service. All of them were treated with chemo and/or hormone therapy, plus 100 UMRC salmon calcitonin a day for 20 days a month until a clinical improvement was observed. The parameters for evaluation were: radiography and scintigraphy of the skeletal segment involved, blood calcium, alkaline phosphatase, intensity of pain, and restriction of function. An assessment was made before and after calcitonin management. Blood calcium fell in all cases even in the range of those initially normal. Alkaline phosphatase decreased in 83.3% and pain disappeared or was less severe in 87.50%. Good results were also observed with regard to restriction of function. Good recalcification of some osteolytic lesions was noted in 7 cases (17.5%). Calcitonin thus proved effective in the correction or prevention of damage caused by hypercalcaemia, and was particularly useful in the reduction of pain and functional damage. Its analgesic effect often appeared at an early stage.

[The possible evaluation of immunity with the DNCB skin test in relation to blast transformation of lymphocytes]. / Possibili valutazioni immunitarie del test cutaneo al DNCB in rapporto alla blastizzazione linfocitaria.

55 patients with various types of malignant neoplasias at different stages were given DNCB skin tests in the Oncological Department of the S. Paolo Hospital in Savona. Lymphocyte blastisation was evaluated both before and after the skin test. In about 75% of the patients it was observed that DNCB sensitisation increased lymphocyte blastisation capacity independently of the level of reaction to the skin test, the type of neoplasia or the patients' age. Indeed increased blatisation was more noticeable in non-responsive DNCB. The hypothesis is advanced that DNCB has the capacity indirectly to stimulate blastisation by unknown mechanisms.

[The DNCB skin test and its comparison with the radioimmunological determination of CEA in some types of neoplasms]. / Considerazioni sullo skin-test al DNCB e suoi raffronti comparativi con il dosaggio radioimmunologico del CEA in alcuni tipi di neoplasie.

The personal series consists of 140 cancer patients followed up over a period of some 3 years and submitted prior to the start of treatment to the DNCB skin test. This test indicates the patient's immune condition and the degree of reactivity shown may be useful prognostically for assessing the course of the disease and its response to immunochemotherapeutic treatment; this was confirmed in 77% of case. The skin test has now been personally associated with CEA radio-immunological metering for patients suffering from breast, lung and digestive system cancer (40 cases in all). The hypothesis, which is supported by the results obtained, is that there is a correlation between CEA titre and skin reactivity to the immunostimulus; in effect, high CEA titres have generally always corresponded to little or no DNCB skin reactivity and vice versa.