Role and efficacy of intraoperative evaluation of resection adequacy in conservative breast surgery.

In the present study we considered the histology of 51 patients who have undergone breast conservative surgery and the related 54 re-excisions that were performed in the same surgical procedure or in delayed procedures, in order to evaluate the role of intraoperative re-excisions in completing tumor removal. In 13% of the cases the re excision obtained the resection of the target lesion. In this study, the occurrence of residual neoplastic lesions in intraoperative re-excisions (24%) is lower than in delayed re-excisions (62%; P = .03). The residual lesions that we could find with definitive histology of re excision specimens are related with lesions with ill defined profile. In 77% of the cases of re excision with tumoral residual the lesion was close to the new resection margin, thus the re-excisions couldn't achieve an adequate ablation of the neoplasm. Invasive or preinvasive nature of the main lesion resected for each case and the approach to the evaluation of the first resection specimen adequacy (surgical or radiological) don't affect the rate of tumoral residual in intraoperative re-excisions. In conclusion, our data are consistent with a low efficacy of intraoperative re excision in obtaining a complete removal of the tumor; intraoperative radiologic evaluation of the first resection specimen is however imperative in defining the effective removal of the target lesion.

[Serotype distribution of Streptococcus pneumoniae isolated from invasive infections at the Hospital de Niños of Santa Fe]. / Distribución de serotipos de Streptococcus pneumoniae aislados de infecciones invasoras en el Hospital de Niños de Santa Fe.

The serotype distribution of Streptococcus pneumoniae varies through time. The introduction of pneumococcal conjugate vaccines showed a decreased prevalence of pneumococcal invasive isolates belonging to serotype 14 and an increase of serotypes not therein included. In 1993, the Hospital de Niños of Santa Fe began surveillance of the serotype distribution of invasive S. pneumoniae disease. In the period 2003-2005, 76 isolates were analysed by studying the correlation between serotype and pathology, age and MIC of penicillin. Serotype 14 was the most frequent followed by serotypes 1, 6B, 18C, 7F, 19 F and 5. Serotype 14 showed a statistically significant correlation with MICs of penicillin ranging from 0,5 to 2 mg/l. Although this serotype was more frequently observed in pneumonia than in meningitis, there was not a significant association with any particular pathology. Serotypes 14 and 1, were prevalent among children under and over 2 years old, respectively. Most of these isolates with MICs of penicillin = 2 mg/l, were from patients with pneumonia and not with meningitis. The serotype distribution was similar to that during the period 1993-99, with the exception of serotypes 18C, 4, 12F and 22F which had never been found before. The emergence of these serotypes makes it essential to continue surveillance to determine which conjugated vaccine formulation would be suitable to prevent the most frequent pneumococcal invasive infections.

Distribución de serotipos de Streptococcus pneumoniae aislados de infecciones invasoras en el Hospital de Niños de Santa Fe / Serotype distribution of Streptococcus pneumoniae isolated from invasive infections at the Hospital de Niños of Santa Fe.

Con la introducción de vacunas conjugadas antineumocócicas se observó, en muchos países, disminución de aislamientos de Streptococcus pneumoniae del serotipo 14 y aumento de aislamientos correspondientes a serotipos no incluidos en esas vacunas. En 1993, el Hospital de Niños de Santa Fe comenzó la vigilancia de la distribución de serotipos de Streptococcus pneumoniae invasores. En este trabajo se estudió la correlación entre serotipo y a) patología (neumonía/meningitis), b) edad (menor o mayor de dos años), y c) CIM de penicilina, para los serotipos aislados en el período 2003-2005. El serotipo predominante fue el 14, seguido del 1, 6B, 18C, 7F, 19F y 5. El serotipo 14 mostró asociación estadísticamente significativa con valores de CIM de penicilina entre 0,5 y 2 mg/l, no así con alguna patología, aunque se lo halló con mayor frecuencia en neumonías que en meningitis. Los serotipos 14 y 1 prevalecieron en niños menores y mayores de 2 años, respectivamente. La CIM de penicilina = 2 mg/l se observó más en neumonías que en meningitis. La frecuencia relativa de los diferentes serotipos hallados fue semejante a la observada en el período 1993-99; no obstante, los serotipos 18C, 4, 12F y 22F no se habían encontrado antes. La aparición de nuevos serotipos convierte en importante la vigilancia, dada la necesidad de formular vacunas que los incluyan y que efectivamente prevengan las infecciones neumocócicas más comunes.

The serotype distribution of Streptococcus pneumoniae varies through time. The introduction of pneumococcal conjugate vaccines showed a decreased prevalence of pneumococcal invasive isolates belonging to serotype 14 and an increase of serotypes not therein included. In 1993, the Hospital de Niños of Santa Fe began surveillance of the serotype distribution of invasive S. pneumoniae disease. In the period 2003 - 2005, 76 isolates were analysed by studying the correlation between serotype and pathology, age and MIC of penicillin. Serotype 14 was the most frequent followed by serotypes 1, 6B, 18C, 7F, 19 F and 5. Serotype 14 showed a statistically significant correlation with MICs of penicillin ranging from 0,5 to 2 mg/l. Although this serotype was more frequently observed in pneumonia than in meningitis, there was not a significant association with any particular pathology. Serotypes 14 and 1, were prevalent among children under and over 2 years old, respectively. Most of these isolates with MICs of penicillin = 2 mg/l, were from patients with pneumonia and not with meningitis. The serotype distribution was similar to that during the period 1993-99, with the exception of serotypes 18C, 4, 12F and 22F which had never been found before. The emergence of these serotypes makes it essential to continue surveillance to determine which conjugated vaccine formulation would be suitable to prevent the most frequent pneumococcal invasive infections.

Radiography of the surgical specimen in early stage breast lesions: diagnostic reliability in the analysis of the resection margins.

PURPOSE: The purpose of this study was to evaluate the diagnostic reliability of specimen radiography in the assessment of the status of resection margins in early stage breast lesions. MATERIALS AND METHODS: The study involved 123 consecutive patients who underwent breast-conserving surgery for early stage breast lesions. Specimen radiography in the two orthogonal views and with direct magnification was obtained in all cases to assess presence or absence of the lesion, position of the lesion within the surgical specimen and direction in which to extend the excision in cases of lesions located close to the margin. Diagnostic reliability was evaluated for only 102 patients with malignant lesions. RESULTS: Comparison between the radiological and histological diagnoses before immediate reexcision had 66% sensitivity, 86% specificity, 74% positive predictive value and 81% negative predictive value. Definitive histological assessment of margin status, including status after reexcision, was infiltrated margins in 23 patients (23%) and clear margins in 79 patients (77%). Definitive histological assessment in 12/19 patients (63.15%) with intraoperative reexcision, confirmed margin infiltration of the first specimen. Twenty patients (20%) underwent a second surgical procedure. CONCLUSIONS: Specimen radiography was reliable in identifying clear margins (74% positive predictive value) and reduced the rate of reintervention from 31% to 20%. Better results will be provided by digital mammographic equipment.

Evaluation of a nested-PCR assay for Streptococcus pneumoniae detection in pediatric patients with community-acquired pneumonia / Evaluación de una PCR anidada en pacientes pediátricos para diagnóstico de neumonía neumocócica adquirida en la comunidad

The aim of the present work was to evaluate the usefulness of a simplified method for DNA extraction coupled to a nested-PCR protocol, based on the amplification of pneumolysin gene fragments for the diagnosis of pneumococcal pneumonia in pediatric patients with clinical and radiological evidence of bacterial infection. Bacterial DNA was extracted from sera by boiling and used without further purification in the PCR for the pneumolysin gene. None toxic reagents were used and the necessary steps to obtain the DNA were left at a minimum; furthermore, it overcomes the use of expensive commercial kits for DNA purification. The total procedure can be completed the same day of sampling and, most important, it avoids the use of sophisticated technology. Both in vitro analytical specificity and sensitivity (10 CFU/ml) of the assay were similar to those previously reported. When clinical samples were tested, the rate of positivity was shown to be 83.3% and 71% in pediatric patients with positive (group a) and negative blood cultures (group b), respectively. In group a, DNA detection was successful in samples from children without treatment or with less than 48 h of antibiotic therapy. None amplification was obtained from sera patients with viral infection or in samples from healthy controls. The application of the strategy described in this paper substantially seems to improve the diagnostic process in a determinate group: blood culture-negative children with pneumonia.

El objetivo del presente trabajo fue evaluar la utilidad de un método simplificado para extracción de ADN, acoplado a un protocolo de PCR anidada, basada en la amplificación de fragmentos del gen de la neumolisina para el diagnóstico de neumonía neumocócica en niños con evidencias clínicas y radiológicas de infección bacteriana. El ADN bacteriano fue extraído del suero por calentamiento y utilizado en la PCR para el gen de la neumolisina sin purificación posterior. Para la obtención de ADN no se utilizan reactivos tóxicos ni costosos "kits" comerciales. El procedimiento completo puede ser realizado en el día y lo que es más importante, evita el uso de tecnología sofisticada. La especificidad analítica in vitro y la sensibilidad (10 UFC/ml) del ensayo fueron similares a lo hallado en publicaciones anteriores. El porcentaje de muestras positivas fue del 83,3% y del 71% en los pacientes con hemocultivos positivos (grupo a) y negativos (grupo b), respectivamente. En el grupo a, sólo se obtuvieron resultados positivos mediante la PCR anidada en los pacientes no tratados o con menos de 48 hs de tratamiento antibiótico. No se obtuvieron señales de amplificación en los sueros de los pacientes con infecciones virales ni en las muestras del grupo control. La aplicación de la estrategia descripta incrementa la posibilidad diagnóstica de neumonía neumocócica en niños con hemocultivos negativos.

Evaluation of a nested-PCR assay for Streptococcus pneumoniae detection in pediatric patients with community-acquired pneumonia.

The aim of the present work was to evaluate the usefulness of a simplified method for DNA extraction coupled to a nested-PCR protocol, based on the amplification of pneumolysin gene fragments for the diagnosis of pneumococcal pneumonia in pediatric patients with clinical and radiological evidence of bacterial infection. Bacterial DNA was extracted from sera by boiling and used without further purification in the PCR for the pneumolysin gene. None toxic reagents were used and the necessary steps to obtain the DNA were left at a minimum; furthermore, it overcomes the use of expensive commercial kits for DNA purification. The total procedure can be completed the same day of sampling and, most important, it avoids the use of sophisticated technology. Both in vitro analytical specificity and sensitivity (10 CFU/ml) of the assay were similar to those previously reported. When clinical samples were tested, the rate of positivity was shown to be 83.3% and 71% in pediatric patients with positive (group a) and negative blood cultures (group b), respectively. In group a, DNA detection was successful in samples from children without treatment or with less than 48 h of antibiotic therapy. None amplification was obtained from sera patients with viral infection or in samples from healthy controls. The application of the strategy described in this paper substantially seems to improve the diagnostic process in a determinate group: blood culture-negative children with pneumonia.

Evaluation of a nested-PCR assay for Streptococcus pneumoniae detection in pediatric patients with community-acquired pneumonia.

The aim of the present work was to evaluate the usefulness of a simplified method for DNA extraction coupled to a nested-PCR protocol, based on the amplification of pneumolysin gene fragments for the diagnosis of pneumococcal pneumonia in pediatric patients with clinical and radiological evidence of bacterial infection. Bacterial DNA was extracted from sera by boiling and used without further purification in the PCR for the pneumolysin gene. None toxic reagents were used and the necessary steps to obtain the DNA were left at a minimum; furthermore, it overcomes the use of expensive commercial kits for DNA purification. The total procedure can be completed the same day of sampling and, most important, it avoids the use of sophisticated technology. Both in vitro analytical specificity and sensitivity (10 CFU/ml) of the assay were similar to those previously reported. When clinical samples were tested, the rate of positivity was shown to be 83.3

and 71

in pediatric patients with positive (group a) and negative blood cultures (group b), respectively. In group a, DNA detection was successful in samples from children without treatment or with less than 48 h of antibiotic therapy. None amplification was obtained from sera patients with viral infection or in samples from healthy controls. The application of the strategy described in this paper substantially seems to improve the diagnostic process in a determinate group: blood culture-negative children with pneumonia.

Lymphatic mapping in early stage breast cancer: comparison between periareolar and subdermal injection.

The combination of preoperative lymphatic mapping with intra-operative probe detection is becoming the standard procedure for identifying tumour lymphatic spread at the time of initial treatment in breast cancer. There are a number of identification techniques for sentinel lymph nodes, but the concordance of the results of a sentinel lymph node biopsy with axillary lymph node dissection did not vary significantly among them. Periareolar (p.a.) injection of tracer is a new procedure specifically studied to overcome some limitations of other techniques; in two groups of patients with early breast cancer we compared the periareolar with the subdermal technique. One hundred and fifty biopsy proven breast cancer patients were consecutively enrolled in this study. This population was divided into two groups: (1) group A, including 100 cancers; lymphatic mapping was performed by s.d. injection of both blue dye and radiotracer; and (2) group B, including 50 cancers; lymphatic mapping was performed with a combination of blue dye injected p.a. and radiotracer injected s.d. For group A, with both techniques we identified one or more SLNs in 100/100 tumours; blue dye detected the SLNs in 99/100 cancers (99%), lymphoscintigraphy in 93/100 cancers (93%). The concordance rate was 92%. For group B, with both techniques we identified one or more SLNs in 49/50 cancers (98%); blue dye detected the SLNs in 48/50, lymphoscintigraphy in 46/50 cancers (92%). The concordance rate was 92%. In the present study p.a. and s.d. injection of blue dye give similar and comparable results. The periareolar technique is simpler and has several advantages over the subdermal technique.

Sentinel node detection in breast carcinoma.

AIMS AND BACKGROUND: The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. METHODS AND STUDY DESIGN: In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors > 2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. RESULTS: We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patient showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. CONCLUSIONS: At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.

Sentinel lymph node and breast cancer staging: final results of the Turin Multicenter Study.

AIM OF THE STUDY: Validation of the sentinel node (SN) technique in breast cancer by means of lymphoscintigraphy. MATERIALS AND METHODS: From December 1996 to January 1999 102 T1-T2 breast carcinoma cases were recruited in Turin. 99mTc-human serum albumin colloids were injected subdermally the day before surgery (mean activity, 5.2 +/- 2.5 MBq). Scintigraphic imaging was performed after injection. After identification of the SN during surgery by a hand-held gamma probe, the SN was excised and sent for histologic examination. SN histology was compared with that of other axillary nodes. RESULTS: The SN detection rate was 86.3%; among 88 cases with an identified SN, 37 (42%) had axillary metastases; the SN was metastatic in 35 cases (sensitivity, 94.6%); in 51.3% of pN+ cases (19/37) the SN was the only metastatic site. In two of the 53 negative SNs, SN histology did not match with that of the remaining axilla (negative predictive value, 96.2%; staging accuracy, 97.7%). CONCLUSIONS: Our results agree with those reported in the literature; however, except in clinical trials and experienced structures axillary lymph node dissection should not be abandoned when mandatory for prognostic purposes, considering that at present SN biopsy alone is not completely accurate for axillary staging, especially in the absence of an adequate learning period.

Heterogeneity of [3H]-mepyramine binding sites in guinea pig cerebellum and lung.

The nature of histamine receptors in peripheral tissues is still controversial. However, evidence of heterogeneous classes of binding sites for [3H]-mepyramine are reported in the literature. The aim of our study was, therefore, to investigate the nature of this heterogeneity by comparing [3H]-mepyramine binding in a central tissue (cerebellum) and in a peripheral tissue (lung) obtained from guinea pigs and to assess its dependence upon the temperature of incubation. The results revealed that the [3H]-mepyramine interaction in both tissues is temperature-dependent. At 25 degrees C, the interaction between [3H]-mepyramine and the receptors was biphasic in the lung while only a single class of binding site was found in the cerebellum. At 0 degrees C, [3H]-mepyramine interacted with three binding sites in the lung and two in the cerebellum. The behaviour of the reference compounds (clemastine, promethazine and histamine) also supported this temperature-dependence. Moreover, two new compounds (DF 11062 and DF 11113), synthesized in our laboratories and endowed with antihistamine activity, can differentiate between the low affinity site seen at 25 degrees C in the lung and that seen in the cerebellum at 0 degrees C.

Antihistaminic/antiallergic activity of 2-dialkylaminoalkylthio(oxy)-1-substituted benzimidazoles: evaluation "in vitro" and "in vivo".

A new series of 2-dialkylamino-alkylthio(oxy)-1-substituted benzimidazoles synthesized in our laboratories was found to have promising antihistaminic activity. The results of pharmacological screening ("in vitro": radioreceptor binding and isolated organs; "in vivo": protection against mortality induced by histamine or by compound 48/80, passive cutaneous anaphylaxis, and prolongation of barbiturate-induced sleeping-time) gave clear-cut structure-activity relationships. This series of products has a general selectivity towards H1 receptors, weak antiallergic properties and negligible central effects. DF 10967 (1-ethoxyethyl-2-dimethyl-aminoethylthiobenzimidazole) was the most interesting compound, being very potent both "in vitro" (Ki = 3.2 +/- 0.8 nM) and "in vivo" (ID50 11 micrograms/kg, i.p. and 8 micrograms/kg, i.p. against histamine- and 48/80-induced mortality), with no central effects. The last finding is probably due to poor penetration into the brain (as confirmed by "in vivo" binding test with [3H]-mepyramine) and to lack of interaction with other central receptors.

Synthesis and pharmacological screening of new phenylpiperazinepropane derivatives and their enantiomers.

Enantiomers of phenylpiperazinepropane-1,2-diol derivatives were synthesized with the purpose to obtain a better antitussive activity/sedative effect ratio. (S)-isomers showed better pharmacological profiles than (R)-isomers and corresponding racemates. Among the (S)-isomers, the unsubstituted compound, levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), has the most favourable antitussive activity/sedative effect ratio and was selected for pharmaco-toxicological evaluation.

Surgical strategy management following lymph nodal positivity at the three levels (a retrospective and perspective study).

The purpose of this study is to evaluate the type of distribution, regular or irregular, of metastases in lymph nodes of I, II and III level. We inted also to establish if the levels of lymph nodal areas represent an evaluation index of prognostic risk more effective than other ones. The results evidenced that in 19.2% of all the classes N+ metastases were not increasing regularly from the level I to the level III. The influence of seven factors on disease free survival has been evaluated: pT, pN, number of metastatic nodes, ER+ or ER-, PgR+ or PgR-, grading, metastatic level at axillary lymph nodes. The present report points out that only the extent of tumor and lymph nodal level have a statistically significant influence on disease free survival. Comparison among disease free survival curves stage N0 with N+ at I level and with N+ at II level revealed that there is no significant difference of survival among these classes, while the comparison between the first 3 classes and N+ at III level is statistically significant.

Synthesis and antibacterial activities of new (alpha-hydrazinobenzyl)cephalosporins.

Some (alpha-hydrazinobenzyl)cephalosporins, I (R = Me, CH2OAc, Cl) and II (R = Me, CH2OAc), structurally related (formula; see text) to cephalexin, cephaloglycin, and cefaclor have been prepared and evaluated in vitro for their antimicrobial activity. The synthesis involves the condensation of the chloride hydrochloride III (R = H or Me) with the 7-aminocephem derivatives IV. The hydrazino compound I (R = Cl), an analogue of cefaclor, resulted in being the most active compound of the series.

[Arterial chemotherapy of tumors. Considerations on 159 cases]. / Chemioterapia arteriosa dei tumori. Considerazioni su una casistica di 159 casi.

The results obtained in 153 patients suffering from advanced primary, residual, recurrent and metastatic cancers localized mainly in the cervico-cephalic district and in other sites (skin, extremities and pelvis, liver, thoracic wall, breast) in whom locoregional intraarterial chemotherapy was employed from 1967, are reported. In order of frequency, the commonest antiblastics used were Methotrexate, 5 FU, Vincristin and DITC. Long-term results show an average remission of 52% and mean survival of 11.4 months; these values are liable to wild fluctuations in relation to various factors such as site, development, state of regional lymph nodes, and any previous surgical, radiation or antiblastic therapy. Intraarterial treatment is found to have the best effect in cases of cancer which have not previously been subjected to any therapy at all, and which involve the cervico-cephalic districts, the liver and melanomas.