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Biomedical subjects

A Molino

Publications and source records attributed to A Molino.

At least 37 records · Page 2Linked to original sources

Ki-67 immunostaining in 322 primary breast cancers: associations with clinical and pathological variables and prognosis.

Cell-proliferation markers are very important in the clinical management of cancer patients, and the identification of Ki-67 (a monoclonal antibody that recognizes proliferating cells) can make it easier to define the level of proliferative activity. This study investigated the associations between the Ki-67 levels measured by means of immunohistochemistry, and other clinical and pathological variables and prognosis in 322 breast-cancer patients. A significant association was found (p < 0.001) between Ki-67 values and tumor size, nodal status, estrogen and progesterone receptor status; multivariate analysis showed that Ki-67 levels were associated with disease-free and overall survival, thus confirming that it is an independent prognostic variable. Various statistical approaches were used in an attempt to establish the best cut-off point for dividing patients into groups at high or low risk of relapse but, in this series, we could find no evidence leading to a single "best" cut-off point. We conclude that the quantitative level of Ki-67 could be used as a prognostic factor in breast-cancer patients.

Breast Neoplasms↗

Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis.

BACKGROUND: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. PATIENTS AND METHODS: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2-4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15-62): 22 patients relapsed and 7 died. RESULTS: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33-6.86) and 0.93 for DFS (95% CI: 0.35-2.45). CONCLUSIONS: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.

Antibodies, Monoclonal↗

Prognostic significance of estrogen receptors in 405 primary breast cancers: a comparison of immunohistochemical and biochemical methods.

Over the last few years, estrogen receptor determination by means of immunohistochemistry has been extensively used. The aim of this study was to compare this technique with estrogen receptor determination by means of dextran-coated charcoal, and to evaluate whether one of the two methods is more predictive of prognosis. Estrogen receptors were determined by means of both the dextran-coated charcoal method and immunohistochemistry in 405 patients with primary breast cancer; age, pathological tumor size, nodal status, and progesteron receptors by dextran-coated charcoal method were also recorded. The disease-free and overall survival probabilities were estimated using the product-limit method; Cox's proportional hazard model was used to evaluate the prognostic role of estrogen receptors as determined by the two methods. There appears to be a close association between estrogen receptor determination by the two methods (81.5% of concordant results) and their prognostic role was similar, even when the patients were divided into different groups (on the basis of their estrogen receptor status) and adjustments for the effect of other prognostic variables were taken into account. Our study shows that the two methods can be used indifferently to evaluate estrogen receptor status as a prognostic factor in breast cancer patients.

Antibodies, Monoclonal↗

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma.

The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( < or = 25% of stained cells) or high ( > 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3-58). Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( > or = 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analysis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.

Adult↗

[Proposal of new formulas for three-point urea kinetics, compared with traditional kinetics and direct dialysis quantification].

Classical urea kinetic model (UKM) has been followed by several proposals to determine dialysis adequacy either by direct quantification (DDQ), either by simplified two-points formulas (pre- and post-dialysis BUN), or by mUKM, a modified three-point algorithm (pre-post and pre-next dialysis), where urea distribution volume is input to obtain clearance and urea generation rate. Our new formulas (mUKM2) are derived from urea mass balance, and avoid iterative calculation: their results are similar to those obtained by UKM and mUKM when the standard post-dialysis BUN value is employed. On the contrary, when the equilibrated net-rebound value (Cpwnr) is employed their results are very close to the reference DDQ model: however the new approach is simpler and more practical, to measure dialysis dose taking account of the urea rebound phenomenon.

Female↗

Estrogen receptors in 699 primary breast cancers: a comparison of immunohistochemical and biochemical methods.

BACKGROUND: Over the last few years, estrogen receptor (ER) determination by immunohistochemistry (ER-ICA) has been extensively used, but it still remains to be established whether this method can replace the standard biochemical technique using dextran-coated charcoal (ERDCC). PATIENTS AND METHODS: ER were determined by both the dextran-coated charcoal (DCC) method and immunohistochemistry (ICA) in 699 patients with primary breast cancer; other parameters (age, pathological T-pT- and nodal status -pN-, progesterone receptors by DCC, proliferative index by ICA) were also recorded. The 'best' cut-off for ERICA was evaluated by means of Receiver Operating Characteristics (R.O.C.) analysis; logistic regression analysis was used to find adequate 'weights' for stain intensity. RESULTS AND CONCLUSIONS: A significant correlation was found between the two methods (p < 0.001). R.O.C. analysis revealed that the 'best' cut-off for the ERICA score was 45% (sensitivity 0.810, specificity 0.804). Logistic regression analysis showed that an ERICA score which also considers staining intensity does not add any useful information concerning ER content in breast cancers.

Breast Neoplasms↗

Mastectomy and immediate breast reconstruction: oncological considerations and evaluation of two different methods relating to 88 cases.

The authors consider 88 cases of mastectomy and immediate breast reconstruction mainly performed using the skin expander plus prosthesis method or latissimus dorsi myocutaneous flaps. At the same time, 53 patients underwent contralateral mastopexy for symmetry. The mean follow-up was 21 months (range 2-102). Progressive disease was observed in nine cases: one patient presented scar relapse, one axillary relapse, two contralateral tumor, two contralateral tumor and distant metastasis, three distant metastases and one death from distant metastasis. Reconstruction complications were capsular contracture in 12 cases, infection in nine, skin necrosis in two, skin expander breakage in three and implant dislocation in one. The final result was judged good in 54 cases, fair in nine, poor in 11 and unevaluable in 14. In conclusion immediate breast reconstruction does not seem to interfere with the disease or oncological therapy. After analysing separately, and comparing the results and complications of the two main techniques used, latissimus dorsi seems to be the most reliable method in the majority of cases but skin expanders can be a good technique in patients with small and firm breasts and without complicating risk factors.

Adult↗

Cisplatin pharmacokinetics using a five-day schedule during repeated courses of chemotherapy in germ cell tumors.

Total and ultrafilterable platinum (Pt) disposition was investigated during 49 courses of chemotherapy in 13 patients with germ cell tumor treated with cisplatin (DDP), 20 mg/m2/day on 5 consecutive days. The following pharmacokinetic parameters were analyzed: distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives, total body clearance (ClT), renal clearance (ClR), and areas under the concentration versus time curve (AUCs). Blood samples were collected immediately before and after DDP infusion (Day 1 through Day 5); in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h after DDP infusion. Urine was collected during each day of treatment and up to 48 h after the last DDP dose. During each chemotherapy cycle plasma levels of total and ultrafilterable Pt progressively increased from the first to the last day of treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46 micrograms/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117 to 0.205 micrograms/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels immediately postinfusion increased from 0.67 +/- 0.20 microgram/ml at the first cycle (first day of therapy) to 1.13 +/- 0.21 microgram/ml at the same time point at the fourth cycle. Mean total Pt peak levels were reached at the end of infusion on the last day of each cycle, and increased from 1.46 +/- 0.29 microgram/ml (first cycle) to 1.89 +/- 0.40 microgram/ml (fourth cycle). Total Pt was detectable in plasma before the beginning of all cycles following the first. As a result, AUC significantly increased and ClR significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis.

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term treatment with methotrexate in patients with corticosteroid-dependent bronchial asthma.

Controlled short-term studies (< 6 months) have yielded conflicting results as to the steroid-sparing effect of methotrexate (MTX) and its effectiveness in treating patients with chronic corticosteroid-dependent asthma (CDA). In an open study, we treated 13 patients with MXT (7.5-20 mg.week-1) for > or = 12 months (range 54-72 weeks). After 12 weeks of treatment, the intake of steroids had fallen by 36 +/- 22% (mean +/- SD); the clinical score was not significantly different from baseline (1.7 +/- 0.44 vs 1.4 +/- 0.52). At 52 weeks, steroid intake was reduced by 87 +/- 23% and 9 of the 13 patients no longer required corticosteroids. Moreover, both the clinical and functional scores were significantly better with respect to run-in values forced expiratory volume in one second (FEV1) 75 +/- 6 vs 60 +/- 10% predicted; forced vital capacity (FVC) 84 +/- 10 vs 77 +/- 13% pred; arterial oxygen tension (PaO2) 11.3 +/- 1.0 vs 10.7 +/- 1.3 kPa (84.5 +/- 7.8 vs 80.6 +/- 9.6 mmHg). No serious side-effects were recorded during the study; transaminase levels were increased in 62% of cases. In patients affected by chronic corticosteroid dependent asthma, the steroid-sparing effects of methotrexate and clinical improvement were apparent after 6 months treatment.

Adult↗

On-line dialysate urea monitor: comparison with urea kinetics.

The outputs of a new on-line dialysate urea monitor (UM) were compared to a urea kinetic model (UKM) and to dialysis direct quantification (DDQ) in 13 patients. As for urea extraction and predialysis urea level, a good degree of correspondence was found between UM and laboratory data. Kt/VUM (1.21) is intermediate between Kt/VUKM (1.28) and Kt/VUKM using the post-rebound urea value (1.14) or Kt/VDDQ (1.14). Passing and Bablok regression analysis indicated no systematic error between Kt/VUM and Kt/VDDQ. The percentage differences in nPCR by UM, UKM and DDQ were not significant, but the standard deviations were wide. The UM approach is very simple and practical, avoiding blood sampling, laboratory analysis and data handling. It is reliable enough for clinical practice. Compared with traditional urea kinetics, Kt/V computation by a mathematical elaboration of the dialysate urea profile drawn from several points theoretically invites fewer errors due to the analytical procedure.

Adult↗

Cisplatin pharmacokinetics in elderly patients.

The treatment of elderly patients with cancer may be difficult because of the narrow therapeutic index of antineoplastic drugs, the decline in the performance of organs and functions, and frequent comorbidity. In these patients, therapeutic drug monitoring may be useful in optimizing chemotherapy. Six patients older than 70 years with a variety of solid tumors received a total of 21 cycles of cisplatin (DDP)-based chemotherapy program (DDP dose, 50-65 mg/m2). Total and ultrafilterable platinum (Pt) were determined in plasma and urine during the first cycle of the therapy by means of atomic absorption spectroscopy. Pharmacokinetic parameters were analyzed with use of a two-compartment open model. The treatment was generally well tolerated. The most important side effects were a significant increase in serum creatinine level (from 0.98 to 1.23 mg/dl) and a decrease in creatinine clearance (from 44.4 to 38.9 ml/min) in comparison with pretreatment values. The mean decrease in hemoglobin levels was slight. The values of the main pharmacokinetic parameters of total Pt agreed well with the data obtained with other adult patients. Total and ultrafilterable Pt had a short distribution phase (t1/2 alpha = 0.35 and 0.54 h, respectively) followed by a prolonged elimination phase (t1/2 beta = 63.08 and 58.91 h, respectively). A reduced ability to clear ultrafilterable Pt (ClT = 123.52 ml h-1 kg-1) was evident and, as a result, the area under the curve increased (15.47 mg h L-1). The limited number of patients and the concomitant use of other agents prevent any firm conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Role of monocytes in cryoglobulinemia-associated nephritis.

Several monocyte-macrophage functions were found to be defective in cryoglobulinemic patients. Nevertheless, monocytes actively phagocytizing cryoglobulins have been frequently found in kidney specimens from these patients. Whether subsequent degradation of the ingested immune material is effective, however, is still unknown. Monocytes from eight cryoglobulinemic patients (4 with active disease and associated nephritis and 4 inactive cases without nephritis) and eight normal controls of same sex and similar age were analyzed. Monocytes from patients with active cryoglobulinemia and associated nephritis were found to be able to ingest, but unable to catabolize, cryoglobulins, as shown by electron microscopy using gold-labeled goat IgG to human IgG and IgM in 18-hour cultured suspensions. Synthesis and maturation of monocyte cathepsin D, one of the most important lysosomal proteases, were analyzed in the same subjects. Purified monocytes were cultured in presence or absence of cryoglobulins for 18 hours at 37 degrees C in RPMI medium and labeled with 35S-methionine. The various forms of cathepsin D were separated by electrophoresis and visualized by fluorography. Results from cultures of monocytes from clinically active cryoglobulinemic patients with nephritis suggest that intracellular transport of newly synthesized cathepsin D was impaired and the release into the medium of precursor polypeptides of the enzyme enhanced in each experimental condition. Since procathepsin D is susceptible to activation in pathologic conditions lowering local pH (such as in inflamed tissues), these data suggest that monocytes from patients with active cryoglobulinemia and associated nephritis have a propensity to exert phlogistic effects via secretion of procathepsin D in tissues.

Adult↗

Nimesulide in the treatment of chronic bronchitis.

Hypersecretion of mucus is the main feature of chronic bronchitis and is associated with an increased susceptibility to bronchial infections. Although airway inflammation is present in patients with chronic bronchitis and is recognised as a contributing factor in the development of bronchial hyper-reactivity and obstruction, the role of anti-inflammatory drugs in the treatment of chronic bronchitis has not been established. Nimesulide is a nonsteroidal anti-inflammatory drug that can modulate the function of neutrophils and block the effects of several inflammatory mediators. We found that a 3-week treatment course of nimesulide in patients with chronic mucus hypersecretion decreased sputum viscosity, thus significantly improving symptoms. The effect of nimesulide on the rheological properties of mucus was slower and weaker than that of classic mucolytics and was more likely to be related to a reduction in bronchovascular permeability. The clinical usefulness of nimesulide in chronic bronchitis deserves further investigation.

Anti-Inflammatory Agents, Non-Steroidal↗

The detection of IgG against a specific mycobacterial antigen (A60) in the diagnosis of tuberculous pericarditis.

Diagnosis of tuberculous pericarditis (TP) is often difficult with standard methods, while prompt recognition of this disease may affect its prognosis. We report a case of tuberculous pericarditis, in which the presumptive diagnosis was obtained by detection of specific immunoglobulin G (IgG) against A60 antigen, the main thermostable component of purified protein derivative (PPD). Serological diagnosis may be a useful approach in the screening of the aetiology of pericarditis.

Aged↗

Serum and intracellular detection of cytokines in patients undergoing chronic hemodialysis.

Tumor necrosis factor (TNF) was detected, before and after dialysis, in sera from 69 patients and, at various times during dialysis, in 28 patients carefully selected for the absence of intercurrent illness. Blood samples were also sequentially collected for separation of monocytes, and cells were sonicated to detect intracellular TNF. Compared with serum levels obtained from 41 healthy subjects, basal TNF values of the unselected group of 69 patients were significantly higher (p < 0.01), independent of the dialyzer membrane. A significant increase in TNF levels by the end of dialysis was found only with Cuprophan (p < 0.01). In the selected group of 28 patients, no significant changes in TNF values were observed in sequential samples. However, a significant increase of intramonocyte TNF levels was found in Cuprophan patients (p < 0.025). Soluble interleukin-2 receptor (IL-2R) levels, measured in parallel in sera from unselected and selected patients, were found to be very much higher than healthy controls without significant changes during the dialysis procedure. While the diverse profiles of TNF obtained from differently selected patients suggest that mechanisms other than membrane biocompatibility play a role in the appearance of these low cytokine levels, the possible nature of uremic toxin for soluble IL-2R can be envisaged by detection in dialysis patients.

Adult↗

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.

Breast Neoplasms↗