Hypokinetic cardiomyopathy. A possible result of myocardial contusion

Myocardial contusion is a frequent complication of blunt chest trauma. Ventricular involvement is generally segmental and exhibits a favourable evolution. We describe the case of a 44-year-old male who suffered an acute blunt thoracic injury with a consequent stable worsening of his functional class. His first electrocardiographic examination 30 days after the trauma showed negative T wave in V3-V6 leads while one and two-dimensional echocardiography exhibited a diffuse damage of the morphology of the left ventricle and a lowering of the fractional shortening (FS) of its end-diastolic diameter (EDD): FS = 23%, EDD = 6.9 cm, diastolic eccentricity index = 65%, systolic eccentricity index = 70%. During a follow-up period of thirteen months ECG became normal after a short time while the echocardiogram maintained its initial abnormalities and the patient maintained his compromised functional class. We report this peculiar pattern of myocardial contusion evolution which has not previously been described.     

The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients

Background: The prognostic implications of p53 accumulation, bcl-2immunoreactivity and tumour proliferative fraction in ovarian carcinomas arestill debated.Patients and methods: One hundred twelve ovarian carcinomas wereimmunostained for p53 protein, for bcl-2 and for the cell cycle-associatedKi-67 antigen. The immunostaining results were correlated with conventionalclinico-pathological variables, response to induction chemotherapy, andpatient survival.Results: p53 accumulation and bcl-2 immunoreactivity in more than10% of neoplastic cells were detected in 61 (54.5%) and 42(37.5%) cases, respectively. A positive correlation between p53accumulation and high (more than 30% neoplastic cells) MIB1 labellingindex (r = 0.235; P = 0.015) was ascertained, whereas no significantassociation was found between bcl-2 immunoreactivity and p53 accumulation orMIB1 labelling index. Both p53 accumulation and MIB1 immunoreactivitycorrelated significantly with a reduced overall survival, but the associationwas lost in multivariate analysis. However, patients with tumourssimultaneously showing p53 accumulation and MIB1 labelling index higher than30% had significantly reduced overall survivals, in both univariate andmultivariate analyses.Conclusion: The simultaneous evaluation of p53 accumulation and MIB1labelling index has independent prognostic implications in common epithelialmalignancies of the ovary, irrespective of the disease stage.     

A freeze-fracture study of the human nail plate

Summary This study of freeze-fracture replicas of human nail plate fragments demonstrates that keratin filaments have a width of about 100 Å. The marginal band is probably formed by a row of particles, 50 Å in diameter, arranged along the inner surface of the plasma membrane. These particles are often masked by keratin filaments. In nonjunctional areas, the plasma membranes are devoid of membrane-associated particles. The only type of junction observed is the desmosome. Even though the modes of keratinization are different, the structures of the keratin pattern, of cell membranes, and of the desmosomes are identical in replicas of wholly keratinized nail and human stratum corneum cells. The ultrastructural differences observed appear to be related to the barrier function carried out by the epidermis and by its desquamation process.     

Endometrial hyperplasia and endometrial carcinoma induce a vasoproliferative response in the chick embryo chorioallantoic membrane

Ten specimens of endometrial adenocarcinoma, of endometrial hyperplasia and uterine prolapse (the latter used as controls), respectively, were grafted onto the chick embryo chorioallantoic membrane (CAM) to investigate their angiogenic activity. The vasoproliferative response was assessed four days after grafting on histologic sections by a planimetric point-count method. Microvessel counts in the CAM area under and around the implants were significantly higher in endometrial adenocarcinoma than in endometrial hyperplasia and in the latter over the controls. These findings show that endometrial hyperplasia and endometrial adenocarcinoma are angiogenic. These results confirm previous observation that angiogenic activity is both a marker of the passage between preneoplastic to neoplastic status and an event that influences tumour progression.     

Clinical role of technetium-99m sestamibi single-photon emission tomography in evaluating pretreated patients with brain tumours

One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with^99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.Preliminary results were presented at the 6th World Nuclear Medicine and Biology Congress (Sydney, October 1994) and at the 42nd Annual Meeting of the Society of Nuclear Medicine (Minneapolis, June 1995).     

Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. METHODS: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.     

A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

Background: Gemcitabine and docetaxel have been claimed to be active single agents in advanced pancreatic cancer. We determined the maximum tolerable dose of docetaxel combined with a weekly fixed dose of gemcitabine and assessed the activity of this combination in advanced pancreatic cancer.Patients and methods: Phase I. Patients were treated with gemcitabine on days 1 and 8, every three weeks, at a fixed dose of 1,000 mg/m²; docetaxel was given at escalating doses starting from 70 mg/m² on day 8. Phase II. In accord with the optimal two-stage phase II study design, 18 patients were treated with gemcitabine (1000 mg/m²) and the maximum tolerable dose of docetaxel (70 mg/m²).Results: Phase I. Dose-limiting toxicities occurred at the second dose level of docetaxel (80 mg/m²), with all three patients developing grades 3 or 4 neutropenia. Consequently, the dose tested in the phase II study was 70 mg/m². Phase II. In the 18 patients enrolled in the study, we registered only one partial response. The time to progression was 3 months, and the median treatment survival was 5.4 months. Grade 3–4 toxicities consisted of neutropenia (three episodes) and thrombocytopenia (two episodes). Furthermore, 10 patients complained of grade 3 fatigue.Conclusions: The addition of docetaxel to gemcitabine does not appear to be useful in advanced pancreatic cancer, since gemcitabine alone achieves similar results.     

67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer

Experimental studies have shown that the 67-kDa laminin receptor (LRec) is an important molecule for the interaction of tumour cells with the extracellular matrix, and that it plays a role in the early steps of angiogenesis and in tumour invasion and metastasis. We performed a multi-parametric study in 171 node-negative breast cancers, followed for a median time of 6 years, to verify whether determination of the LRec provides prognostic information in addition to intra-tumoral microvessel density (IMD), a measure of tumour angiogenesis, and to other biological and conventional indicators. A positive association between LRec expression and high neovascularization was found, although it did not reach significance. LRec was not associated either with other biological markers (oestrogen receptor, progesterone receptor and p53 expression) or to the conventional prognostic features [menopausal status, tumour size, histological types, grading and peri-tumoral lymphatic vessel invasion (PLVI)]. In univariate analysis, IMD, p53, PgR, PLVI, grading and tumour size were significant prognostic indicators of relapse-free survival (RFS). LRec expression approached significance when considered as a dichotomous variable, after having selected the optimum cutoff of 10% to distinguish high-risk from low-risk patients. For overall survival (OS), tumour size and IMD (continuous variable) were significant prognostic factors, and p53 approached significance. In multivariate analysis for RFS, the joint variable LRec and vascularization was the strongest independent prognostic factor, followed by PgR, PLVI and p53. For OS, tumour size was the only independent prognostic indicator in this series.