Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis.

All currently available and approved therapies for osteoporosis inhibit bone resorption. But, despite their great value, antiresorptive agents are generally not associated with dramatic increases in bone mass. In light of these data, the aim of our prospective, placebo-controlled, randomized clinical trial, with a 3-year follow up, was to examine the effects of cyclic intravenous pamidronate and fluoride in combination, versus pamidronate alone, on bone mineral density (BMD) at vertebral and femoral levels, biochemical markers of bone turnover, IGF-1 serum levels, and safety and tolerability in 40 postmenopausal women with osteoporosis. During the treatment period, pamidronate alone reduced both markers of bone formation and bone resorption, resulting in an increase of BMD, after 3 years, of 7.07% at the lumbar level and of 6.76% at the femoral level. In the group treated with pamidronate and fluoride, markers of bone turnover had a different trend: after 3 years, there was a lower reduction of bone resorption and an increase of bone formation markers, with a concomitant increase in IGF-1 levels. This resulted, after 3 years of treatment, in a marked variation of BMD at the lumbar level (+12.74%) and a reduced, but still significant, increase at the femoral level (3.89%). Spine radiography and clinical evaluation did not reveal any vertebral fractures in either treatment group. In conclusion, the combined use of pamidronate and fluoride produced somewhat larger, continuous increases in BMD, at the lumbar level, than pamidronate alone.

Morphometric assessment of nucleolar activity in liver cells during the evolutive pathway of chronic hepatitis C to cirrhosis.

Using a computer-assisted image analysis system, we performed a morphometric study of silver-stained nucleoli of hepatocytes in liver biopsy specimens from hepatitis C virus-positive patients with chronic persistent hepatitis (3 cases), chronic active hepatitis (4 cases), and cirrhosis (4 cases). The number and the total area of nucleoli, the average area of each nucleolus and the nuclear area were determined for each of 100 hepatocytes per case. A continuing increase in the area of both nucleoli and nuclei paralleled a progressive decrease in the number of nucleoli during the evolution of chronic hepatitis C to liver cirrhosis. These findings would indicate that the hepatitis C virus-induced liver damage causes reactive changes in surviving hepatocytes resulting in an increased nucleolar biosynthetic activity rather than in an increment of cell proliferation rate. Therefore, the liver response to hepatitis C virus injury seems to be mainly based on a condition of cell "hypertrophy", whereas we previously showed that a process also of compensatory hyperplasia occurs in chronic hepatitis B, possibly resulting from a different pathogenesis of the viral damage.

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.

Changes in nucleolar transcriptional activity in hepatitis B virus-associated chronic liver diseases. Preliminary results from a quantitative study of silver-stained nucleoli.

Modifications of gene expression may occur in hepatitis B virus (HBV)-related chronic liver diseases, possibly also involving ribosomal RNA (rRNA) genes contained in the nucleolus. Changes in the level of transcriptional activity of rRNA genes are reflected by variations in the number and/or size of the nucleoli. Therefore a quantitative analysis of the silver-stained nucleoli (AgNus) was performed in a small series of liver needle biopsies from patients with HBV+ chronic persistent hepatitis (CPH) (n = 3), HBV+ chronic active hepatitis (CAH) (n = 3) and HBV+ cirrhosis (CIR) (n = 3). In each case, 100 hepatocytes were selected. The number of the nucleoli (AgNuN), their total area (tAgNuA), the average area of each nucleolus (xAgNuA), the nuclear area (NA) and the percentage ratio of tAgNuA related to NA (rAgNuA) were determined for each hepatocyte nucleus. The pooled mean values of all the features were significantly different (p less than 0.001) among the case groups. The results point towards a remarkable increase of nucleolar activity in CAH in comparison with CPH, whereas an additional increment of this activity is associated with the progress from CAH to CIR.

Cytologic diagnosis of malignant mesothelioma in serous effusions using an antimesothelial-cell antibody.

Differentiating mesothelioma, reactive mesothelium, and adenocarcinoma in serous effusions is often difficult, despite the application of ancillary techniques in support of the traditional cytomorphologic criteria. A polyclonal antimesothelial-cell antibody recently developed by our group was evaluated as a histogenetic marker on a series of primary (n = 12) and metastatic (n = 12) malignant effusions. Immunostaining was performed on paraffin sections from cell blocks. All mesothelioma effusions stained positive for the antibody, whereas, in contrast, all metastatic carcinoma specimens failed to react. These results (100 percent specificity and 100% sensitivity for mesothelioma) provide a basis for a reliable use of the antibody in the cytologic examination of suspicious or malignant serous effusions.

Use of monoclonal antibody B72.3 as a marker of metastatic carcinoma cells in neoplastic effusions.

The value of monoclonal antibody B72.3 as a diagnostic discriminator between mesothelioma and carcinoma cells in malignant effusions was assessed using the ABC method in a series of cell blocks prepared from centrifuged fluids. These were obtained from either pleural or peritoneal neoplastic effusions in patients with histologically verified malignant mesothelioma (n:10) or carcinoma (n:20). Reactivity with MAb B72.3 in at least 10% or more of tumour cells was found in 16 (80%) out of 20 metastatic carcinoma, whereas 2 mesotheliomas displayed positive immunostaining in less than 5% and approximately 20% of the malignant cells respectively. Reactive mesothelial cells were consistently non-immunostained. These results suggest that B72.3 positivity in greater than 10% of tumour cells is certainly indicative, but not absolutely diagnostic, of a metastatic origin of malignant effusions.