Biomedical subjects
Publications and source records attributed to R Costanzo.
The antifungal activity of methanolic extract and alkaloidal fraction of Berberis aetnensis against Candida species was investigated. The crude extract was active against Candida species, this activity being higher than that of the alkaloidal fraction and berberine.
Propolis is produced by bees and is reported to have several pharmaceutical properties. Its antibacterial activity against strains causing upper respiratory tract infections is particularly important: propolis might be used as a therapeutic agent to prevent the bacterial infections that sometimes overlap viral infections. In this study the in vitro activity of both an alcoholic solution and a hydroglyceric extract of propolis, as well as its active principles, was tested against bacteria responsible for respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes). We also evaluated the in vitro activity of a combination of propolis and its active principles and some beta-lactams, macrolides and fluoroquinolones. Our results, though not demonstrating a clearly synergistic activity between antibiotics and propolis and its constituents, show the possibility of using natural preparations, due to their antimicrobial and anti-inflammatory properties, to enhance antibacterial therapy.
The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.
Previous research showed that berberine-containing Berberis species synthesise the substances 5'-methoxyhydnocarpin-D (5'-MHC-D) and pheophorbide a, which have no antimicrobial activity but inhibit the expression of multidrug resistant efflux pumps (MDRs) in Staphylococcus aureus and potentiate the action of berberine. The MDR pumps extrude synthetic and natural antimicrobials from bacterial cells. We searched for these compounds in Berberis aetnensis C. Presl. (Berberidaceae), an endemic plant of the volcano Mount Etna. This work confirms the presence of pheophorbide a and permits us to hypothesise the presence of 5'-MHC-D in leaf extracts. In fact, the activity of ciprofloxacin was improved when two chromatographic fractions isolated from leaf extracts were added. These results are indicative of the presence of MDR pump inhibitors. Moreover, crude extracts were tested on several micro-organisms and showed antimicrobial activity mainly against Gram-positive bacteria and yeasts.
BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.
BACKGROUND: Gemcitabine is active in patients with otherwise resistant or refractory ovarian cancer. As the drug is well tolerated, studies using gemcitabine combined with other antineoplastic agents are needed. The aim of the study was to determine the maximum tolerated dose (MTD) of epirubicin combined with gemcitabine, with and without support of G-CSF. PATIENTS AND METHODS: Patients with platinum-resistant or refractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800 mg/m2 day 1 and 8; 200 mg/m2 escalation per level) and epirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2 escalation per level) were given every 21 days for four to six cycles. G-CSF (filgrastim 5 microg/kg/die) was given in case of grade 4 neutropenia (levels without support) or from day 9 up to leukocyte count > 10.000/mm3 after nadir (levels with support). Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. MTD was determined first without and then with G-CSF. RESULTS: Four levels were studied (G 800 + E 60; G 1000 + E 60; G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and three patients enrolled, respectively. DLT (grade 4 febrile neutropenia) was observed in two patients at level 3. Thus, G1000 + E 60 mg/m2 was the MTD without G-CSF. The addition of prophylactic G-CSF did not allow a further increase of the dose and grade 4 thrombocytopenia was the DLT at level 4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in four patients. Among the 13 patients with measurable or evaluable disease, 3 partial responses were observed for an overall response rate of 23.1%. CONCLUSIONS: The combination of gemcitabine 1000 mg/m2 (day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasible therapy. Grade 4 neutropenia is frequent and G-CSF support is often required. With prophylactic support of G-CSF, the DLT is thrombocytopenia.
Second-line treatment of patients with metastatic breast cancer resistant to anthracyclines is an important clinical issue. The aim of the present two-stage phase II study was to evaluate activity and toxicity of vinorelbine + mitomycin C (VM) in such patients. Fifty-five patients were entered and received vinorelbine 30 mg/m(2) on days 1 and 8 + mitomycin C 10 mg/m(2) on day 1, every 4 weeks, up to 9 cycles. Two complete and 23 partial responses were observed for an overall response rate of 45.4% (95% CI 32.0-59.4). Median survival was 13 months and probability of surviving after a 1-year follow-up was 58%. Toxicity was never life-threatening, but G-CSF was used in 45% of cycles to contrast neutropenia that was the most frequent side effect. These results are consistent with previous studies and strongly support VM being considered among the optimal polychemotherapy regimens for second-line treatment of metastatic breast cancer in clinical practice; for clinical research aims, VM should be used as control arm for randomized trials evaluating the activity of new drugs against breast cancer.
Fluconazole inhibition of Saccharomyces cerevisiae S288c growth was evaluated in media containing ammonia, L-proline or L-leucine as a nitrogen source. Growth inhibition by fluconazole was maximum when L-proline was used as a nitrogen source, while rhodamine 6G accumulation and fluconazole resistance were the highest when ammonia was the sole nitrogen source.
The aim of this study was to investigate the possible influence of arteriovenous fistula (AVF) on nerve conduction velocity in patients on intermittent hemodialysis and its relevance to the pathogenesis of carpal tunnel syndrome (CTS). The data on 22 patients showed no statistically significant differences in the electrographic parameters considered. This suggests that AVF by the end-to-end method plays no significant part in the alteration of nerve conduction. Possibly radial steal phenomena, which occur with other types of AVF, are at least partly responsible for the reported cases of CTS.
The kinetics of sodium across dialysis membranes were studied during diffusion and during convection utilizing cuprophan and cellulose hydrate membranes. During diffusion the changes in plasma water sodium concentration are correlated to the sodium concentration gradient between plasma water and dialysate but an increase also occurs when the gradient is annulled, due to the Donnan effect. During convection the plasma water sodium concentration increases during the passage through the dialyzer and the ultrafiltrate sodium concentration is significantly lower than the plasma water sodium concentration; this is due to the fact that the plasma proteins, as anions unable to cross the membrane, affect the kinetics of the sodium cations. Therefore, during diffusion the kinetics of sodium are mainly affected by the sodium concentration gradient and by the plasma protein concentration, while during convection the plasma protein concentration is the main factor affecting the kinetics of sodium.
Explore the source record for details and available documents.
Other investigations have demonstrated that pressure, exerted by fluid contained within the lumen of the closed neural tube, plays an important role in the morphogenesis of cranial regions of chick embryos. In this study, we investigated whether this pressure is involved also in the formation of the secondary portion of the neural tube--the portion formed by canalization of a solid mass of cells. To determine this, the posterior neuropore was prevented from closing (resulting in myeloschisis localized to he lumbosacral region) by removing the portion of the vitelline membrane covering the embryo, and reincubating for various periods. Secondary neurulation occurred normally in embryos exhibiting lumbosacral myeloschisis, demonstrating that this process occurs autonomously in chick embryos. Additional experimental studies are needed to ascertain what specific mechanisms cause the secondary portion of the neural tube to form.
A substrate labeled fluorescent immunoassay procedure for serum theophylline has been automated. The method uses the Ames (SLFIA) substrate-labeled fluorescent immunoassay reagents and Technicon AutoAnalyzer equipment. Forty-seven sera analyzed for theophylline by the automated Ames SLFIA procedure and by the Syva EMIT method yielded the regression equation y (Ames) = 0.92x (Syva) + 0.47, SE, sy.x = 1.67, and correlation coefficient r = 0.934. Recoveries ranged from 94.6 to 100% by the automated SLFIA method. Within-run mean and SD for a sample in and above the therapeutic range was 14.5 +/- 0.37 and 22.7 +/- 1.0 mg/L, respectively. Day-to-day reproducibility was 13.4 +/- 0.92 and 24.7 +/- 1.71 mg/L for a sample in and above the therapeutic range, respectively. The automated SLFIA procedure analyzes serum for theophylline at the rate of 40 per hour and gives results comparable to the Syva EMIT method. The same equipment was also used for the SLFIA determination of phenytoin and phenobarbital and yielded reliable results. The manifold and equipment were the same. The only change was the substitution of the Ames phenytoin and phenobarbital reagents for the theophylline reagent.
Forty three uremic patients on regular hemodialysis treatment (4 hours 3 times/week) were dialyzed for a period of 28.95 +/- 14.46 months with a dialysate sodium concentration (NaD) of 142 mEq/l, similar to their plasma water sodium concentration corrected for the Donnan factor ("physiological" NaD). Blood pressure (BP) and body weight (BW) dropped significantly. During two following periods, lasting 18 and 14 months, with NaD 148 mEq/l, similar to the patients' plasma water sodium concentration ("pharmacologically high" NaD), cardiovascular stability improved and BP did not show significant increase. Using "physiological" and "pharmacologically high" NaD the removal of water and sodium by convection improves the cardiovascular stability and the patients' well being, without bringing about the feared long-term cardiovascular side effects, if an appropriate dry body weight is achieved, because of better correction of the cellular overhydration.
Explore the source record for details and available documents.
Forty-three uraemic patients were studied for 60.95 +/- 14.46 months of haemodialytic treatment (4 hours, 3 times/week). After a first dialysis period of 28.95 +/- 14.46 months with a dialysate sodium concentration (NaD) of 142 mEq/L blood pressure (BP) and body weight (BW) showed values significantly lower (p less than 0.001). During a following period of 32 months with NaD 148mEq/L BP did not show significant changes. A more 'physiological' removal of water and sodium by convection does not bring about the feared long term cardiovascular side effects if an appropriate dry BW is achieved, probably because of better correction of the cellular overhydration.
Four patients with acute renal failure due to myeloma (IgG with lambda, lambda, lambda, IgG with kappa) were studied; serum creatinine was 4.7, 5.9, 4.25, 10.8 mg%, and proteinuria 2.1, 2.8, 5.2, 4.2g/24h respectively. Renal biopsy specimens (3 patients) showed interstitial fibrosis, oedema, infiltration of mononuclear cells, tubular atrophy or dilatation with many 'myeloma kidney' casts. The patients were treated with plasmapheresis (2-4 exchanges) and methylprednisolone pulses (three to four 1g pulses). Maintenance therapy included prednisone, vincristine, melphalan and cyclophosphamide. After a follow up of 26, 17, 8, 6 months respectively, serum creatinine levels are 1.7, 2.4, 1.8, 4.2mg% respectively. Proteinuria disappeared after three months of therapy in 3 patients, and then remained absent for the successive follow up.
Micropuncture studies in rats and dogs have provided evidence for a cause-and-effect relationship between peritubular protein concentration and proximal tubular reabsorption (PTR). If this effect is obtained in man, hypoalbuminemia in nephrotic syndrome should lead to a fall in PTR. Sodium excretion, however, is very low in nephrotic patients; but this sodium retention may be due to distal over-reabsorption. Glucose may be used as a marker of PTR. Because of the linkage between glucose and sodium, glucose reabsorption is expected to be suppressed when PTR of sodium is suppressed. Glucose titration studies were performed in 21 patients with chronic glomerulonephritis without renal failure divided in three groups: I (six patients) with serum albumin greater than 3 g/100 ml; II (five patients) with serum albumin of 2 to 3 g/100 ml; and III (10 patients with edema and nephrotic syndrome) with serum albumin less than 2 g/100 ml. The minimum threshold for glucose decreased in nephrotic patients (group III), and its fall was related directly to hypoalbuminemia. The splay of titration curve was markedly increased in group III when compared to the titration curves of patients without nephrotic syndrome (groups I and II). The splay point was 0.78 in group I, 0.52 in group II, and 0.37 in group III. These data provide evidence that glucose reabsorption is decreased in nephrotic syndrome and are consistent with a fall in PTR in nephrotic syndrome.