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Biomedical subjects

A Savarese

Publications and source records attributed to A Savarese.

At least 19 recordsLinked to original sources
PubMed2002

Perspectives in the clinical management of BRCA mutations carriers.

The recent identification of the breast cancer-associated genes BRCA1 and BRCA2 is changing the clinical care provided to women at high-risk of breast cancer. We briefly review what is currently known about the clinical management of individuals who bear (or are suspected of bearing) genes mutations and which are the prevention strategies that would reduce the incidence and mortality of breast cancer in this subset of women.

Breast Neoplasms↗
PubMed2000

Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor.

The aim of our study was to explore whether nerve growth factor (NGF) plays any role in the development of peripheral neuropathy induced by anticancer treatment. We measured the circulating NGF levels in 23 cancer patients before and after chemotherapy. We evaluated whether the development of peripheral neurotoxicity was associated with changes in basal NGF concentrations in patients studied with a comprehensive neurological and neurophysiological examination. The results of these studies showed that the circulating levels of NGF, which are about 20 pg/ml in plasma of controls, decrease during chemotherapy and in some cases completely disappeared after prolonged treatment with antitumor agents. The decrease in NGF levels seems to be correlated with the severity of neurotoxicity. These results clearly suggest that NGF might become a useful agent to prevent neuropathies induced by antineoplastic drugs and restore peripheral nerve dysfunction induced by these pharmacological compounds.

Aged↗
PubMed1995

A phase II trial of vinorelbine and thiotepa in metastatic breast cancer.

BACKGROUND: Vinorelbine as single-agent has achieved an overall response rate of > 20% as second-line treatment and 40%-50% as first-line treatment. The aim of this study was to evaluate the activity and toxicity of the combination of vinorelbine and thiotepa as second-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-three patients (31: anthracycline-based chemotherapy, 16: high-dose epirubicin) were given vinorelbine 30 mg/m2 and thiotepa 12 mg/m2 d 1 and 8 every 21 days. RESULTS: Among the 32 evaluable patients two complete responses and seven partial responses were observed, for an overall response rate of 28% (C.I. 12-44). The median duration of response was 9 months and the median time to progression 6 months. Significant toxicity was primarily leukopenia (72%); anemia was also frequent (48%) as well as local phlebitis (39%). CONCLUSION: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines.

Adult↗
PubMed1995

DNA ploidy, proliferative index, and epidermal growth factor receptor: expression and prognosis in patients with gastric cancers.

BACKGROUND: The 5-year survival rate of patients with stomach cancer is usually around 20%. The clinico-pathological features that are presently used to assess patient prognosis are not sufficient to define gastric tumor behavior. Therefore, an accurate analysis of different biological characteristics of gastric cancer cells could allow the course of disease to be predicted and may help to improve treatment strategies. EXPERIMENTAL DESIGN: The prognostic values of DNA ploidy, proliferative activity and epidermal growth factor receptor (EGF-R) expression were studied in gastric tumors from a series of 63 patients. DNA ploidy and proliferative activity, evaluated in terms of DNA index (DI) and proliferative index (PI), respectively, were determined by flow cytometry on paraffin-embedded tumor tissues. EGF-R expression was detected by immunohistochemistry on paraffin-embedded tumor sections of the same specimens. The clinico-pathological and the biological parameters were then correlated, and the patients overall survival was calculated using a chi-square test and the Kaplan-Meier method. RESULTS: DNA ploidy abnormal cell clones were found in 44% of cases (median DI = 1.4, range 1.04-2.5). Aneuploid tumors showed high PI more frequently than diploids (71% versus 36%, p = 0.01). The analysis of the expression of EGF-R revealed that 88% of aneuploid tumors were positive for receptor expression. On the contrary, diploid tumors showed the presence of EGF-R only in 56% of cases (p = 0.01). DI, PI, and EGF-R expression were not related to histological grade. Conversely, the three biological parameters were significantly correlated to clinical stage and tumor invasion. The Kaplan-Meier survival curves showed a 73% 5-year survival rate in patients with diploid tumors whereas only 33% of patients with aneuploid lesions had a good prognosis (p = 0.001). CONCLUSIONS: We demonstrate that DNA ploidy, PI, and EGF-R expression are closely related to some pathological and clinical characteristics in gastric cancer. The close relationship between aneuploidy, EGF-R positive expression, node involvement, and tumor invasion suggests that these parameters may be indicators of high malignancy. Finally, the results also show that aneuploidy and EGF-R-positive expression are indicative of a worse prognosis in gastric cancer patients. The study of these parameters might allow a more accurate stratification of patients, so that a targeted therapeutic protocol may be defined.

Aged↗
PubMed1994

Association of cumulus-oocyte complexes with the intrafollicular levels of a blood protein in Bubalus bubalis.

The protein pattern of the follicular fluid (FF) and the ultrastructure of the inner cumulus-oocyte complex (COC) has been analysed in single antral follicles (n = 146) of buffalo B. bubalis ovaries. The protein population of FF was fractionated by SDS-PAGE; the resulting pattern was Coomassie stained and processed for densitometry. Comparative analysis of sera and autologous FFs showed a marked difference in the level (measured as the percentage of total proteins) of one 21 kDa polypeptide band, called 'L'. Concentration of L, which was mainly higher in the serum (2.05 +/- 1.5%) than in the surrounding FF (0.98 +/- 0.94%), fluctuated widely in fluids from the same ovary. On gel filtration of FF and SDS-PAGE of the fractions collected, the L polypeptide was found and eluted together with a 36 kDa polypeptide, called 'H', with an exclusion volume lower than that of albumin. The levels of both polypeptides in the eluted fractions were measured by gel densitometry, and the same ratio H/L was found (2:1). These data suggest that H and L are subunits of a complex high-molecular-weight protein. The presence of L levels in male sera comparable to those detected in females indicates that this putative protein does not originate in the ovary but is transported from the blood. Moreover, a correlation between the increase in the percentage of Lf (calculated as %L in FF/%L in serum) and atresia was observed. COCs (n = 86) obtained during the collection of the single FF samples were processed for transmission electron microscopy. The ultrastructure of each COC was compared with the SDS-PAGE data of the associated FF. Healthy COCs were found to be related to very low levels of Lf (between 0 and 14% of those measured in serum). COCs with an early atretic ultrastructure undetectable at the dissection microscope, were associated with FFs having Lf levels between 24% and 60%; advanced atresia was associated with Lf values up to 70%. Finally, the acrosome reaction of buffalo precipicitated spermatozoa in vitro was monitored by adding one volume of FF with high (FF+; Lf = 80%) or undetectable (FF-) values of Lf to the sperm suspension.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrosome↗
PubMed1993

Characterization of cytotoxic activity of saporin anti-gp185/HER-2 immunotoxins.

The oncogene HER-2/neu encodes a trans-membrane receptor of 185 kDa with tyrosine-kinase activity. Over-expression of this molecule has been reported in a significant proportion of human breast and ovarian carcinomas, characterized by a poor clinical prognosis. Two monoclonal antibodies (MAbs), recognizing distinct epitopes of the gp 185 extracellular domain, have been utilized in the present study for the production of immunotoxins (ITs) by conjugation to the type-1 RIP (ribosome-inactivating protein) plant toxin saporin 6 (SAP). These ITs have been shown to retain tumor-specificity and specifically to inhibit protein synthesis in the gp185HER-2(+) SK-BR-3 breast-carcinoma cell line with IC50 values lower then 1 nM. Kinetics of the cytotoxic activity of the ITs are characterized by a slow rate, since incubation times ranging from 24 to 60 hr, depending on the different degree of expression of the receptor, are required to determine > 90% inhibition in the incorporation of radiolabeled leucine. However, the cytotoxic activity of these ITs, as evaluated by a more sensitive clonogenic assay, appears highly potent, since we have observed that 3 to 4 logs of cells are killed upon exposure to the ITs for short times at concentrations ranging from 1 to 5 x 10(-8) M.

Animals↗
PubMed1993

Sample preparation for bivariate flow cytometric analysis of breast tumor specimens.

The availability of monoclonal antibodies (MAbs) raised against functional or phenotypic cell markers can improve the suitability of flow cytometry (FCM) in assessing and validating prognostic parameters of human neoplasia. The major problems encountered in this type of study, when performed on solid tumors, are the recovery of a large and representative number of tumor cells and the possibility of performing a DNA analysis on antigen-selected populations. A panel of MAbs was chosen on the basis of the recognized membrane antigens important to the biologic characterization of human breast cancer cell populations. The possibility of performing bivariate FCM analysis of cell surface antigens and DNA content was investigated on 4 breast tumor cell lines and 10 fresh breast biopsies. Different fixations and tumor disaggregation procedures were considered. The results indicate that ethanol fixation is the most effective procedure for performing biparametric FCM analysis and that a combined enzymatic-mechanical disaggregation procedure applied on breast tumor specimens allows great recovery of intact cells without affecting antigen detection or DNA distribution.

Antibodies, Monoclonal↗
PubMed1993

Remarks on the complications following ACL reconstruction using synthetic ligaments.

The authors analyse the method used between 1983 and 1990 in 161 patients with chronic anterior laxity of the knee treated by 162 ligament reconstructions utilizing synthetic ligament prostheses. Tearing of the prosthetic ligament is the most feared and frequent complication. This may be due to technical error, wear of the material or, to a lesser extent, new trauma. With a follow-up of up to 80 months, the number of tears seems excessively high. This means that artificial ligaments cannot today be considered a satisfactory surgical technique. The considerable technical improvements in autologous reconstructive surgery make the biological approach preferable even today.

Adult↗
PubMed1992

Characterisation of a human glioblastoma cell line (LI) expressing hypothalamic and pituitary hormones.

The human glioblastoma cell line LI showed morphological features typical of its neuroectodermal origin. Cells were positive by immunofluorescence to GFAP, MHC class II, and L1 determinants. Cytogenetic analysis showed the presence of a modal chromosome number of 63, ranging from 58 to 69 chromosomes (DNA index was 1.6). Northern blot analysis demonstrated the presence of mRNA transcripts specific for transglutaminase C (type II or "tissue"), growth-hormone releasing-hormone (GHRH), insulin-like growth factor II (IGF-II), and proopiomelanocortin (POMC). The GHRH mRNA was present in two different sizes, one similar to the normal hypothalamic species of 0.75 kb, whilst the second species was a large transcript of approximately 10 kb size. Treatment with 5 microM retinoic acid or 5 mM alpha-difluoromethylornithine for 5 days sharply reduced the growth rate and also induced modulation of the ultrastructure and antigenic profile. This cell line may be useful to study glial differentiation and the relationship of GHRH, IGF-II and POMC expression with differentiation in neuroectodermal tumours.

Blotting, Northern↗
PubMed1992

Thrombophlebitic complications in arthroscopic surgery of the knee.

Arthroscopic surgery is generally considered to be free of any significant complications. In particular, there is a much lower incidence of vascular complications as compared with open surgery of the knee. A careful examination of the literature, made by the authors, and an in-depth analysis of a significant sample (790 patients over 2 years) out of a total of more than 2200 knee arthroscopies performed over 7 years, has shown that thrombophlebitis is in fact an important complication especially in patients over the age of forty. The need for an accurate preliminary study to identify the patients at risk and for regular and specific out-patient check-ups to prevent the onset of severe vascular and thrombophlebitic complications is stressed.

Adolescent↗
PubMed1991

Production and characterization of two immunotoxins specific for M5b ANLL leukaemia.

We describe the production and functional characterization of 2 monocytic-cell-lineage-specific immunotoxins constructed with saporin emitoxin (SAP) from Saponaria officinalis. Interest in the production of these immunotoxins, of possible clinical relevance, has been raised by the availability of 2 MAbs of high specificity for circulating monocytes and M5b ANLL, thus envisaging their potential use in bone-marrow purging. SAP emitoxin was selected on the basis of the low cytotoxicity in unconjugated form, as opposed to highly specific cytotoxicity and favourable pharmacokinetical properties in the conjugated form. SPDP conjugation produced immunotoxins which retained serological specificity and protein-synthesis-inhibitory activity. The 2 immunotoxins did not interfere with bone-marrow progenitor-cell growth in a CFU-GM colony assay. On the contrary, they were capable of killing monocytic cells selectively, as demonstrated in phenotypical and functional assays. Thus these 2 novel immunotoxins appear to be promising reagents in purging autologous bone marrow prior to transplantation in patients suffering from monocytic leukaemia.

Antibodies, Monoclonal↗
PubMed1991

[Role of echography in the diagnosis and treatment monitoring of congenital acetabular dysplasia. Personal experience with 2000 examined children].

Since 1987 the authors have used sonography (US) as the means to detect dysplasia and congenital dislocation of infant hips, to define severity of the disease, and to monitor the results during treatment. In this paper the authors report their experience in 2000 examined babies. In 20 young patients, mainly females, 25 pathologic joints were detected and classified as 2c-4 hips. Orthopedic treatment employed Pavlick harness and, in case of partial success, Milgram abduction pillow too. This treatment has always been successful, except for a case with severe dislocation with echostructural changes in the acetabular cartilage. In this case, surgery was necessary. "Delayed ossification" (type 2b hips) and physiological immatury (type 2a hips) with alpha angle greater than or equal to 55 degrees were not splinted in abduction: normal maturity has always been attained without dysplastic involutions. Our experience confirmed US value in the early diagnosis of congenital acetabular dysplasia, when clinics exhibited evident limitations. Nonetheless, management and economical problems are still to be solved, due to the relationship of the widespread use of US in infant population and to its successful results, also considering the low incidence of the examined pathologic condition.

Acetabulum↗
PubMed1989

[Cytofluorometric analysis of thymic lymphocytic subpopulations in mice with B-16 melanoma].

Two colour flow cytometric analysis of the Lyt2 and L3T4 T-cell surface antigens on thymocytes from B16 melanoma bearing mice, reveal an altered cell phenotype. At the early stage of the neoplasia and during the growth, the phenotypes Lyt2+/L3T4- (T suppressor) and Lyt2+/L3T4+ (T immature) decrease. Conversely, Lyt2-/L3T4+ (T helper) increase. These findings suggest the hypothesis that impairment of the immune functions in B16 melanoma bearing mice could be due to a primary thymic alteration.

Animals↗
PubMed1989

Osteoid osteoma of the vertebral body. A case report.

The authors describe a case of osteoid osteoma localised in the body of a lumbar vertebra. This rare localisation--the tenth case described in the literature--and its associated drug-dependency and serum positivity for HTL3 justify its addition to the literature. In addition to an accurate history, the diagnosis requires scintigraphy with Tc 99 and CT scan. The latter is needed so that a correct surgical approach may be planned.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Treatment of fractures of the lower limbs with functional braces.

Closed treatment of fractures has recently used the method of functional braces. If well applied, these clear many patients with fractures from indication for surgery. The results reported for 118 cases show the utility and practicability of this method, especially in leg fractures and fractures of the femur with more than two fragments.

Adolescent↗