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Biomedical subjects

A Banfi

Publications and source records attributed to A Banfi.

At least 19 recordsLinked to original sources

Chondrocyte and osteoblast differentiation stage-specific monoclonal antibodies as a tool to investigate the initial bone formation in developing chick embryo.

Taking advantage of monoclonal antibodies raised against chick hypertrophic chondrocytes (BD5, LA5, AD2) and osteoblasts (SB1, SB2, SB3, SB5), we have investigated expression of differentiation stage-specific antigens by further differentiating hypertrophic chondrocytes. Expression of all antigens was developmentally regulated during in vitro further differentiation of hypertrophic chondrocytes and all monoclonal antibodies, including those raised against osteoblasts, recognized antigens synthesized by chondrocytes at specific differentiation stages. In particular, the expression of the SB5 antigen, considered specific for secretory osteoblasts incorporated into the bone matrix, progressively increased during the chondrocyte culture and reached its maximum at the time of matrix mineralization. Interestingly, the SB3 antigen was transiently expressed at an intermediate phase of the culture with a staining pattern characteristic of cell-cell adhesion proteins. When cryosections of the chondro-bone junction of developing embryo tibiae were stained, it was observed that monoclonal antibodies raised against hypertrophic chondrocytes stained frank hypertrophic and elongated chondrocytes (BD5, LA5), a very discrete peripheric layer of cartilage (AD2), and cells embedded in the initial osteoid matrix (LA5), but failed to stain cells in the preosteoblast and osteoblast region. On the contrary, monoclonal antibodies recognizing antigens on the surface of cells in the osteogenic layer surrounding the initial bone, also stained frank hypertrophic and/or elongated chondrocytes on the cartilage side of the initial bone (SB1, SB2, SB3). The SB5 monoclonal antibody, in addition to staining cells in the osteoid, also stained a few chondrocytes immediately adjacent. These observations support the concept that hypertrophic chondrocytes may further differentiate to osteoblast-like cells and participate to the initial bone formation.

Animals

Early stage Hodgkin's disease: ten-year results of a non-randomised study with radiotherapy alone or combined with MOPP.

From September 1976 to June 1982, 201 consecutive patients with stage I (A and B)-IIA Hodgkin's disease were stratified in two groups according to prognostic factors. The F group included 116 patients with favourable presentation: they were staged with laparotomy and treated with subtotal or total nodal radiotherapy alone. The U group included 85 cases with unfavourable presentation who were staged by laparoscopy and treated with 3MOPP (mechlorethamine, vincristine, procarbazine, prednisone)-radiotherapy-3MOPP. At 10 years the F group showed a freedom from progression (FFP) of 71% with significant difference between stage I and II (85% vs. 59%; P = 0.003) and an overall survival of 84%. The results of the U group were: FFP 83%, overall survival 74%, and the findings were not influenced by stage. FFP in patients with bulky vs. not bulky lymphoma was 70% vs. 87% (P = 0.04). No secondary acute non-lymphocytic leukaemia developed among patients treated with radiotherapy and in continuous complete remission, while acute leukaemia occurred in the F group patients who received salvage chemotherapy (4 of 31 cases) and in the U group (3 of 85 cases). Present results confirm the usefulness of radiotherapy alone in favourable pathological stage IA. All other disease stages will require a different strategy that should consist of radiotherapy combined with short-term effective regimens, such as ABVD (doxorubicin, bleomycin, vinblastine and decarbazine) or VBM (vinblastine, bleomycin and methotrexate) to reduce the incidence of MOPP-associated gonadal dysfunction and leukaemogenesis.

Adolescent

C-reactive protein in measles.

Seventy-two children with early measles (1st-3rd day of rash), presenting at two centres in Santiago, Chile, were classified as having mild ('ordinary measles', n = 50), or moderate to severe measles ('primarily severe measles', n = 22). The level of serum C-reactive protein (CRP) was determined by nephelometry from a finger prick sample. The mean CRP value in ordinary measles, 19 mg/l, was significantly lower (P less than 0.001) than in primarily severe measles where the mean CRP was 65 mg/l. During late measles (5th-8th day of rash), the mean CRP was 19 mg/l if the child recovered uneventfully (n = 35), whereas the mean level of 123 mg/l (P less than 0.001) was encountered when the child suffered from complicating pneumonia (n = 22). We conclude that the simple quantitative CRP determination is a useful alarm signal during the course of measles: elevated levels point to severity or complications in recovery.

Amoxicillin

Serum C-reactive protein in childhood meningitis in countries with limited laboratory resources: a Chilean experience.

Quantitative C-reactive protein (CRP) was determined sequentially by nephelometry and photometry from a finger prick serum sample in 67 children with bacterial meningitis (BM) and 16 children with aseptic meningitis (AM). The initial mean CRP value of 180 mg/liter in children with BM differed significantly from the 12 mg/liter found in those with AM (P less than 0.001). In BM a slow descent instead of rapid normalization or a secondary increase in sequential CRP values were early indicators of complications during recovery, such as resistance to the antibiotic. A significant difference in the mean CRP values between uneventful and complicated courses of BM was observed from the fourth day on (P less than 0.001). The measurements obtained with nephelometry correlated reliably with the more widely available photometry (r = 0.99). Easily performed rapid CRP determinations can considerably improve the quality of care in meningitis patients, especially in those situations where facilities for performing bacterial cultures or antibiotic susceptibility testing are not available.

C-Reactive Protein

Malonamic acid derivatives as M1 selective muscarinic receptor antagonists.

A series of malonamic acid esters with suitable amino alcohols, typical of antimuscarinic compounds, was synthesized and the affinities for the three pharmacologically defined muscarinic receptor subtypes, namely M1, M2 and M3, were evaluated by radioligand displacement experiments. It was found that the esters with 3-quinuclidinol 7b, 7f-g, 8 and 9 are ligands with intermediate to high affinity for the M1 receptors, for which they show a preferential binding. Unexpectedly, the ester 7a with tropine bound with negligible affinity to all the receptors investigated. The introduction of a phenyl group on the carboxamido moiety of 7b gave compound 9, which showed an affinity for the M1 receptor comparable with that of the reference drug Pirenzepine 1.

Animals

Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial.

From 1973 to 1980, 701 women with small breast cancer (less than 2 cm in diameter) were randomized into two different treatments. 349 patients received classic Halsted mastectomy and 352 patients received quadrantectomy, axillary dissection and radiotherapy on the ipsilateral breast. 24.6% of the patients in the mastectomy group and 27.0% of the patients in the conservation group had axillary metastases. Overall 10 year survival was 76% in the Halsted patients and 79% in the quadrantectomy patients; 13 year survival was 69% and 71%, respectively. No differences were observed after analysis by site and size of the primary tumour and age of the patients. Patients with positive axillary nodes had consistently better survival curves in the quadrantectomy group compared with the Halsted group (not significant). Among the quadrantectomy patients there were 11 local recurrences (with 4 deaths) while among the Halsted patients, 7 had local recurrences (5 deaths). There were 19 cases of contralateral breast carcinomas in the quadrantectomy group and 20 in the Halsted group. At 16 years from the beginning of the trial no evidence of oncogenic radiation risk was observed. In patients with small size carcinomas total mastectomy should have no role.

Breast Neoplasms

Conservative treatment of early breast cancer. Long-term results of 1232 cases treated with quadrantectomy, axillary dissection, and radiotherapy.

One thousand two hundred and thirty-two women with invasive breast cancer lesions measuring less than 2 cm in diameter, clinically assessed as T1N0-1M0, were treated from 1970 to 1983 at the National Cancer Institute of Milan with quadrantectomy, axillary dissection, and radiotherapy (QUART). Pathologic evidence of lymph-nodes metastases was found in 32% of the patients. Overall survival at 5 and 10 years from surgery was 91% and 78%, respectively. The cumulative probability of survival tends to decrease with increasing tumor size: the 7-year survival rate was 84% in cases in which lesions measured from 1.6 to 2.0 cm, and 94% in cases in which the lesions were less than 0.5 cm. Tumor site in the treated breast did not affect distant outcome. No difference was found between the patients without node metastases and patients with one node involved, whereas the patients with more than one node showed a lower probability of survival. The survival curves of 352 cases treated inside a randomized trial and that of 880 cases routinely treated appear to be superimposable. Local recurrences and new primary ipsilateral tumors were, respectively, 35 (2.8%) and 19 (1.6%); 56 women with local recurrences or second tumors underwent second surgery (total mastectomy, 43; wide resection, 11). Five of them died from distant spread of breast cancer, while 49 are alive and well. In the contralateral breasts 45 carcinomas were recorded during the follow-up time. The results of the present analysis of a large number of T1 cases reconfirm the safety of integrated radiosurgical conservative treatments.

Adult

Hodgkin's disease: the Milan Cancer Institute experience with MOPP and ABVD.

The report includes the essential therapeutic and toxic results following MOPP vs. MOPP/ABVD and MOPP vs. ABVD within a combined modality setting. The findings indicate that in stage IV the alternating regimen is superior to MOPP while in stage IIB-III ABVD plus radiotherapy yielded superior results associated with no treatment-induced sterility and leukemia compared with MOPP plus radiotherapy.

Antineoplastic Combined Chemotherapy Protocols

Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy.

This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols

Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma.

The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.

Adolescent

Contralateral breast cancer after limited surgery plus radiotherapy of early mammary tumors.

Conservative treatment of early breast cancer with limited surgery requires a mandatory irradiation of the affected breast, which implies a low but measurable irradiation of contralateral breast too. As ionizing radiations can produce an oncogenic effect on mammary tissues, the series of 701 patients of the Milano clinical trial on T1 No breast cancer (1973-1980) was investigated to compare the incidence of contralateral breast cancer in the Halsted group (not irradiated) and in the QU.A.RT. group (irradiated on the operated breast with a total dose of 50 Gy plus a limited boost of 10 Gy). In March 1986, a contralateral breast cancer was diagnosed in 17/349 patients (4.9%) of the Halsted group and in 18/352 patients (5.1%) of the QU.A.RT. group after a median follow-up of 108 months. The sites of contralateral cancer were superimposable in the two groups of patients, with a constant prevalence of external quadrants, despite the great difference of dose distribution in the irradiated patients. Our data on the incidence of contralateral breast cancer failed to demonstrate an oncogenic effect of irradiation to date, but the follow-up is still in progress and any future event will be registered and discussed.

Axilla

Comparison of Halsted mastectomy with quadrantectomy, axillary dissection, and radiotherapy in early breast cancer: long-term results.

From 1973 to 1980 we randomly assigned 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy (n 349) or to 'quadrantectomy' with axillary dissection and radiotherapy to the ipsilateral breast tissue (n 352). The two groups were comparable in age distribution, size and site of primary tumor, menopausal status, and frequency of axillary metastases. The average follow-up time was 103 months. Actuarial curves show no difference between the two groups in the disease-free interval after surgery or in the overall survival rate. At 8 yr the disease-free survival was 77% for the patients in the Halsted group and 80% for those in the 'quadrantectomy' group, and the overall survival was 83 and 85% respectively. We conclude that small breast cancers may be safely treated with the conservative treatment described. In our opinion total ablative operations are not justified.

Axilla

Ceftriaxone in the treatment of bacterial meningitis in children.

A total of 24 pediatric patients with a diagnosis of meningitis, confirmed by positive CFS culture, were enrolled in the study. All patients received ceftriaxone in different doses. No difference in clinical outcome was found between the patients who received ceftriaxone twice a day and the 11 who received the drug as a single daily dose. The latter dosage proves to be preferable. The therapeutic outcome in this series of patients was 22 cured and 2 failures. Bacteriological and pharmacokinetic findings are discussed.

Bacterial Infections

Second acute leukemia and other malignancies following treatment for Hodgkin's disease.

The records of 1,329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives.

Acute Disease

Case-control study to identify risk factors for paediatric endemic typhoid fever in Santiago, Chile.

Typhoid fever is an important endemic health problem in Santiago, Chile. Its incidence has more than doubled in recent years, during which access to potable water and sewage disposal in the home became almost universal in the city. A matched case-control study was carried out to identify risk factors and vehicles of transmission of paediatric typhoid fever; 81 children in the 3-14-years age group with typhoid fever were compared with controls, matched with respect to age, sex, and neighbourhood. It was found that case children more frequently bought lunch at school and shared food with classmates. Also, case children more often consumed flavoured ices bought outside the home; none of 41 other food items considered in the study was associated with a higher risk of typhoid fever. Only two food handlers for cases and one for controls were positive for Salmonella typhi, indicating that persons preparing food solely for their own family were not the main source of S. typhi infection. Rather, the risk factors identified in this study are consistent with the hypothesis that paediatric endemic typhoid fever in Santiago is largely spread by consumption of food-stuffs that are prepared outside the individual's home and are shared with or sold to children.

Adolescent

Bone and soft tissue sarcomas in the follow-up of Hodgkin's disease.

Prolonged follow-up of large series of patients treated for Hodgkin's disease with an intensive therapeutic approach has demonstrated an incidence of second tumors of around 5-10%. Acute leukemia is the most frequent second neoplasia, and treatments including alkylating agents and radiotherapy seem to be correlated with a higher risk of this fatal complication. Bone and soft tissue sarcomas have rarely been observed after treatment of Hodgkin's disease, and only a few cases are described in the literature. Four cases observed at the Istituto Nazionale Tumori of Milano in a large series of nearly 800 patients treated over the last two decades with different modalities are presented. One case of chondrosarcoma and 3 cases of soft tissue sarcomas were diagnosed after a median and mean interval of 50 and 70 months, respectively (range 49-96). Three patients had been treated with radiotherapy plus chemotherapy (MOPP, 2 cases; ABVD, 1 case), and one with radiotherapy alone. The site of the second tumor was always within an irradiated area, which had received a dose ranging from 10 to 43 Gy. Prognosis of secondary bone and soft tissue sarcomas is very poor. Three of our cases died 14, 15 and 19 months after diagnosis; only one patient is alive, 3 months after diagnosis of a chondrosarcoma. The problem of second tumors in patients treated for Hodgkin's disease requires a careful evaluation of aggressive treatment modalities to minimize the risks of this severe complication.

Adolescent

Non-Hodgkin's lymphomas of Waldeyer's ring.

From 1970 to 1980, 171 consecutive cases with non-Hodgkin's lymphomas (NHL) of Waldeyer's ring were admitted to this Institute. The cases were reviewed to evaluate whether involvement of Waldeyer's ring might represent a distinct clinicopathologic entity. Adequate pathologic staging was performed in 86% of cases. All slides were reviewed, and the histologic diagnosis given according to the Rappaport classification, the Kiel classification, and the recent Working Formulation of NHL for Clinical Usage. Waldeyer's ring alone was involved in 12.3% of the cases at presentation; regional nodes were positive in one-third (35.7%), and distant involvement was detected in half of the patients (52%). The tonsils represented the most frequent site of involvement by NHL within Waldeyer's ring. Treatments employed were heterogeneous, but most of the patients with stage I-II received radiotherapy alone. The present series shows that the association of involvement of Waldeyer's ring and the stomach by NHL occurs in less than 10% of the cases. Treatment results and patterns of recurrence fail to differentiate NHL involving Waldeyer's ring from those of other sites. Prognosis remains related to the classical variables and is independent of the site of onset.

Humans

[Radiotherapy of Hodgkin's disease in clinical stages I and II A: relapse of the disease and salvage therapy].

The authors describe the results of 71 patients with clinical stage I A (40 patients) and II A (31 patients) primarily treated with radiotherapy alone (61 mantle fields and 10 subtotal-nodal plus spleen irradiation). All patients achieved complete remission at the end of the treatment; 31 (43.7%) patients (15 at stage I and 16 at stage II) relapsed during the follow-up, mostly for nodal or extranodal extensions (87% of relapses). In 21/31 relapsed patients chemotherapy +/- radiotherapy was utilized as salvage treatment. Three patients died for second solid tumors and 1 patient died for jatrogenic late effect (leukemia after 4 cycles of MOPP). Despite the high percent of relapses, the long term overall survival (83.4%) of these patients is quite satisfactory mostly for the efficacy of chemotherapy as salvage treatment. However the authors think that laparosplenectomy plus subtotal-nodal irradiation is the treatment of choice for patients with Hodgkin disease at stage I and II A. Chemotherapy, instead, must be primarily utilized only for patients with a worse prognosis for hilar adenopathies or "bulky" mediastinum.

Adolescent