Effect of early treatment with captopril and metoprolol singly and together on postinfarction left ventricular remodeling.

BACKGROUND: beta-Blockers improve clinical outcome after acute myocardial infarction (AMI), but few data are available on their effectiveness in preventing left ventricular remodeling. The aim of the study was to assess the relative effects of captopril, metoprolol, and their combination on left ventricular remodeling after uncomplicated AMI. METHODS: Two hundred fifty consecutive patients with a first AMI were randomly allocated to receive for 6 months captopril (up to 75 mg/d, group 1), metoprolol (up to 200 mg/d, group 2), or both (group 3) starting within 24 hours from symptom onset. Of these, 130 patients (group 1, 46; group 2, 47; group 3, 37) completed the study; all patients underwent 2-dimensional echocardiography at baseline and after 2 weeks and 3 and 6 months from AMI. RESULTS: At 6 months, in comparison with baseline values, left ventricular end-diastolic area index (LVEDI) significantly increased in group 3 (P =.013) and wall motion score index significantly decreased in group 1 (P =.038). At any follow-up evaluation, the covariance analysis showed significantly greater interval changes in LVEDI in group 3 than in group 1 (P =.0077 at 2 weeks, P =.0108 at 3 months, and P = 0.0155 at 6 months). No significant differences were observed between group 1 and group 2 and between group 2 and group 3. CONCLUSIONS: After uncomplicated first AMI, early and long-term treatment with captopril alone attenuates left ventricular remodeling better than its combination with metoprolol. In the head-to-head captopril versus metoprolol therapy strategy comparison, captopril alone seems more effective in reducing postinfarction enlargement, but a definite difference was not demonstrated.

Effects of early treatment with captopril and metoprolol singly or together on six-month mortality and morbidity after acute myocardial infarction. Results of the RIMA (Rimodellamento Infarto Miocardico Acuto) study. The RIMA researchers.

UNLABELLED: The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess the relative effects of angiotensin-converting enzyme (ACE) inhibition by captopril, beta-blocker therapy by metoprolol, and their combination in patients with a first acute myocardial infarction on: 1. echocardiographically detected left ventricular remodeling; 2. prognosis. The second goal will be the argument of the present paper. Two-hundred fifty < or = 75 years consecutive patients (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1), metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3) starting in the first 24 hours after the onset of symptoms. Intravenous beta-blockers in the acute phase of myocardial infarction and all other cardioactive drugs were allowed. The effect of the randomized therapy at six months from admission to the coronary care unit was considered in relation to: 1. recurrence of spontaneous cardiac events and of elective revascularization procedures; 2. adverse reactions (hypotension, atrioventricular block, cough, allergy, need of beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment modification based on physician's decision. RESULTS: Definite follow-up data were available in 226 patients and 195/226 patients (86%) had a complete treatment period. In these patients (per protocol analysis), 37 spontaneous cardiac events occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven patients received a coronary revascularization procedure. Events occurred in 11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis demonstrated an increased odds ratio (OR) for spontaneous cardiac events in patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective revascularization procedures were statistically less frequent in patients treated with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2 and 3; p = 0.03). The intention-to-treat analysis on the overall population (226 patients) confirmed the presence of a trend towards a higher risk in patients from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the multivariate regression analysis, a trend towards less adverse reactions in patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95% Cl: 0.15-1.13; p = 0.07). CONCLUSIONS: In a randomized early post-infarction treatment strategy, ACE inhibition with captopril alone or in combination with metoprolol demonstrated an increased protection against spontaneous cardiac events at six months in comparison with metoprolol alone. On the other hand, the beta-blocker treatment was associated with a lower number of elective revascularization procedures and appeared better tolerated than ACE inhibition.

[Treatment of prostatic carcinoma in clinical stage C. Comparison between radiotherapy plus hormonal therapy after progression and immediate hormonal therapy]. / Terapia del carcinoma prostatico allo stadio clinico C. Confronto tra radioterapia più ormonoterapia dopo progressione e ormonoterapia immediata.

The optimal treatment of prostate cancer in clinical stage C is controversial. On the one hand a disease still confined by definition, as stage C is, should require a curative therapy such as surgery or radiotheratherapy. On the other hand the known fact that 50% of stages C are pathological stages D1, should propose a palliative, even thou effective, medical treatment. In fact both choices are questionable. A radical treatment risks being insufficient, whereas a palliative does not allow for giving a chance of a theoretically possible cure. In an attempt to resolve this difficulty, a sort of compromise is proposed. The patients should be initially treated with radical radiotherapy, and only in the case of progression will standard hormonotherapy be given. Thanks to this behaviour a possibility of cure is maintained, and, in addition, when suffering a progression the patients are likely to benefit from hormonotherapy owing to the fact that they are not pretreated. From 1985 to 1991 forty-eight clinical stage C patients were observed. They were given the choice between two treatments after explaining the theoretical benefits and disadvantages of both. Treatment A consisted of cobalt-60 therapy followed by hormonotherapy after progression, treatment B in primary ormonotherapy with LH-RH analogue +/- Flutamide. Twenty patients opted for treatment A and 21 for B.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell proliferation in breast carcinoma assessed by a PCNA grading system and its relation to other prognostic variables.

This study was undertaken to relate the expression of the proliferating cell nuclear antigen (PCNA), a proliferation marker of putative prognostic significance, to some more established prognostic factors in a series of 60 consecutive breast cancer surgical specimens. PCNA was detected by the PC10 monoclonal antibody (MAb) using an immunohistochemical method and PCNA immunostaining was estimated on a semiquantitative basis, a cut-off value of 50% of positively stained tumour cells discriminating between the high (> 50%) and low (< 50%) PCNA grade. The PCNA grade did not correlate with tumour size and axillary node status. However, a high PCNA grade tended to be associated with a poor histological grade and there was an inverse relationship with oestrogen-receptor status, as determined by means of the immuno-histochemical staining for the oestrogen-induced pS2 protein. These conflicting results suggest that the possible prognostic usefulness of PCNA immunostaining, as a measure of cell proliferation rate, in breast cancer is yet to be demonstrated and can be validated only by direct relation to survival data.

[Antibiotic prophylaxis in surgery. Results of a 4-year personal case series]. / Antibioticoprofilassi in chirurgia. Risultati di 4 anni su casistica personale.

A prospective study of surgical infections in our Department of Surgery in the years 1986-1989 is reported. 2719 patients entered the study: they represent the total number of patients operated in the above said period (628 urgent and 2091 elective operations). As suggested in 1964 by Altmeier, surgical procedures were classified in four groups according to the potential risk of intraoperative contamination. For every septic complication observed pertinent cultures were performed and responsible pathogens identified. We present our protocol of antibacterial prophylaxis which distinguishes antibiotics given as "ultra short term", "short term", "antibiotic prophylaxis". The results obtained and particularly the total number of infections (3.9%), and the percentage of infections in group 3 (4.6%) and in group 4 (23.1%) procedures validate the usefulness of antibiotic prophylaxis in these patients. In group 1 and group 2 patients the usefulness of antibiotic prophylaxis seems very doubtful.

Ifosfamide and etoposide salvage treatment in advanced ovarian cancer.

Twelve FIGO stage III-IV ovarian cancer patients progressing or relapsing after primary cisplatin-containing combination chemotherapy were treated with ifosfamide and etoposide. Only patients with clinically evaluable disease entered the trial. The 12 patients received a median number of 3 courses (range 1-6). No complete or partial response and two disease stabilizations were observed. Ten patients progressed on therapy. The combination of ifosfamide and etoposide does not appear to be an effective salvage treatment for advanced ovarian cancer.

[Carcinoma of the male breast in the province of Alessandria. Clinico-pathologic aspects of an 8-years' case load]. / Carcinoma della mammella maschile nella provincia di Alessandria. Aspetti clinico-patologici di una casistica di 8 anni.

The authors report their experience on male breast carcinoma based on a series of 16 cases diagnosed between 1981 and 1988 at the City Hospital of Alessandria. Main clinico-pathological findings are described and compared with those recorded in the relevant world literature. Emphasis is placed on the immunohistochemical evaluation of estrogen receptors and the frequency data of this uncommon cancer in hospital-based series are reviewed.

Expression of epidermal growth factor receptor in human breast carcinoma and its correlation with morphological and biological features of tumour aggressiveness.

A series of 54 patients presenting with primary breast cancer were investigated for tumour expression of epidermal growth factor receptor (EGFR) by the indirect three-step immunoperoxidase technique which used the monoclonal antibody EGFR1. The percentage of malignant cells positive for EGFR was determined and scored on a four-point (0-3) scale in each case. EGFR was demonstrated in 35 (64.8%) tumours. EGFR expression did not correlate (p greater than 0.05) with growth fraction immunohistochemically visualized by means of the monoclonal antibody Ki-67, tumour size, axillary lymph node status and malignancy grade. In contrast, a significant inverse relationship (p less than 0.05) was found between EGFR and estrogen receptor (ER) patterns. Expression of EGFR per se does not appear to be relevant to the biological behaviour of breast cancer as revealed through an evaluation of proliferative activity, pathological stage and histological differentiation. Recognition that EGFR is negatively related to ER supports the present evidence that the control of malignant cell growth and differentiation depends on complex regulatory mechanisms in which several extracellular messenger molecules, including hormones and peptide growth factors together with their specific cellular receptors, are involved and inextricably interwoven.

Correlation of proliferative activity with pathological features in breast carcinoma.

A presently undefined nuclear antigen recognized by the monoclonal antibody Ki-67, and the transferrin receptor (TR), both expressed by proliferating cells, were visualized in cryostat sections of 40 consecutive cases of primary breast cancer using a three-step immunoperoxidase technique. The percentages of Ki-67 and TR positive cells were determined. A strong positive correlation was observed between these two indices of proliferation (p less than 0.01). Moreover, each of them was positively related to the histological tumour grade (p less than 0.01), although the scatter in the number of proliferating cells within each grade was large. No significant relation (p greater than 0.05) was found between the percentages of Ki-67 and TR positive cells and tumor size and between these values and axillary node status. These correlations are similar to those recently reported in the relevant literature and suggest that immunohistochemical assessment of proliferative activity may prove to be an objective indicator of biological behaviour and therefore be of clinical and therapeutical importance.

The influence of perimenopausal age on estrogen receptor status and estradiol and DNA content in human breast cancer.

In 25 cases of breast cancer occurring in perimenopausal age, estrogen receptor (ER) content was determined by the dextran-coated charcoal (DCC) assay and both endogenous-bound estradiol and nuclear DNA concentrations were measured by computerized quantitative analysis on formalin-fixed paraffin-embedded tissue samples. No statistically significant relationship (p greater than 0.05) was found within these parameters. The high incidence (64%) of ER-negative cases in this menopausal age was mainly due (62.5%) to interference of high levels of endogenous estradiol occupying the receptor sites in-vivo. The prevalence of hormone-insensitive and aneuploid cell clones accounted for the remaining true ER-negative tumours (37.5%).

[Trends in the combined use of radiotherapy and chemotherapy in oncology]. / Orientamenti nell'associazione radio-chemioterapica in oncologia.

The use of combined radiation and chemotherapy in oncology is designed to improve the long-term results in cancer cases whether subjected to surgical treatment or not. The benefits and risks of this approach are examined and the forms for which such treatment is beneficial are indicated.

[Radiotherapy and integrated treatment in carcinoma of the lung]. / Radioterapia e terapie integrate del carcinoma del polmone.

The results of lung cancer treatment are often disappointing. In order to optimise the use of the therapeutic means at our disposal each clinical case should be assessed on a multidisciplinary basis with regard to the stage and type of the tumour. The fundamentals of radiotherapy technique are presented as are the concepts of integrated radiation, chemical and surgical treatment for the two basic groups of microcytomas and non microcytomas.

[Carcinoma of the male breast and hormone receptors]. / Carcinoma della mammella maschile e recettori ormonali.

The series of cancers of the male breast encountered in Alessandria Hospital in 1981-85 is reported. Estrogen-progestin receptor assays were performed on all patients with results in line with reports in the literature and were used as the basis for the selection of adjuvant post-operative treatment. The good early results appear to confirm the validity of this approach.

Secretory (juvenile) carcinoma of the breast in an adult woman.

A case of secretory (juvenile) carcinoma of the breast is reported in a 31-year-old woman. Secretory carcinoma in adults is rare, only twenty-seven cases previously reported. It is known to have a more favourable prognosis than the conventional ductal carcinoma. The most adequate treatment appears to be a simple mastectomy with low axillary dissection.

Uncommon histological variants of clear cell carcinoma of the ovary. Report of two cases with immunohistochemical and ploidy studies.

Two cases of clear cell carcinoma of the ovary with uncommon histological features are here presented. The former showed considerable formation of giant, hCG-negative tumour cells. In the latter the clear cell pattern was admixed with smaller elements that resembled steroid-hormone secreting cells. However, these cells revealed negative immunostaining for testosterone and a higher degree of DNA content abnormalities than the clear cell component.

Primary renal lymphoma.

A case of primary non-Hodgkin's lymphoma of the kidney is reported. Only 7 previously documented cases have been found in a survey of the relevant literature. Histogenetic hypotheses are reviewed. Ultrasound and computed tomography findings are described and the diagnostic role of these techniques is emphasized.