Possible involvement of androgen receptor alterations in hepatocarcinogenesis.

BACKGROUND: Androgen receptors (ARs) act as transcription factors. An increased AR activity could be due either to mutations or to an increased expression of the receptor. AR mutations involving the hormone binding domain could increase AR function and promote carcinogenesis, as suggested for prostate cancer. AIMS: Herein, we evaluated qualitative (point mutations involving the hormone binding domain) and quantitative AR alterations and their possible correlation with cell proliferation and tumour grading. MATERIALS: Carcinomatous and non-cancerous surrounding liver tissue was collected from 14 Caucasian patients with hepatocarcinoma. They were all affected by cirrhosis with different aetiologies. METHODS: AR missense mutations, AR mRNA and protein levels, AR distribution in the liver, liver cell proliferation, and tumour staging were evaluated by DNA sequencing, quantitative real-time PCR, Western blot analysis, immunofluorescence, PCNA immunostaining, and conventional histological techniques, respectively. RESULTS: AR gene regions encoding the hormone binding domain did not contain any missense mutation. AR mRNA and protein levels were increased in hepatocarcinoma compared to non-cancerous surrounding tissue. Cell proliferation was significantly increased in the tumour compared to non-cancerous surrounding tissue. CONCLUSIONS: Mutations of the AR regions studied were not involved in hepatocarcinogenesis. Elevated AR levels in transformed cells could have a tumour promoting effect by stimulating cell growth.

[Avascular jaw osteonecrosis in a hemodialysis patient treated with bisphosphonates]. / Osteonecrosi avascolare mandibolare in un paziente in trattamento emodialitico sostitutivo trattato con bifosfonati.

Bisphosphonates are molecules derived from pyrophosphates,but, unlike pyrophosphates, they are resistant to enzymatic hydrolysis. Bisphosphonates are used in the treatment of Paget's disease, cancer-related osteolysis, myeloma, primary hyperparathyroidism, and osteoporosis. In dialysis patients bisphosphonates may be used to reduce bone pain due to renal osteodystrophy. We describe the case of a 60-year-old woman with a history of breast cancer who had been on dialysis for 8 years. She had been receiving clodronic acid at 100 mg per week intravenously for the last 2 years. A year ago, the patient underwent surgical extraction of the lower right second molar. Her jaw pain increased in the following days. An orthopanthograph and a CT scan of the head showed osteolysis, and a surgical osteotomy was performed. Histological examination led to a diagnosis of avascular osteonecrosis of the jaw. Avascular osteonecrosis is typically described in the jaw. In this case, prolonged bisphosphonate treatment may have worsened the osteonecrosis.

[Quality in dialysis]. / La qualità in dialisi.

BACKGROUND: Several clinical and laboratory dialysis parameters have been suggested by national and international guidelines. Our study aimed to evaluate a series of quality indicators in the dialytic treatment of a group of patients in our two dialytic centers. PATIENTS AND METHODS: In a population of 159 patients on renal replacement therapy (RDT) we performed a 1-yr prospective observational study, with common parameters to indicate cardiovascular pathologies (PAS, LVMI), calcium-phosphorous metabolism (Ca, PO 4 , Ca x PO 4 ), dialytic adequacy (Kt/V, URR%), nutritional status (nPCR, Alb, K), and anemia (hemoglobin (Hb)). For each parameter we evaluated the mean average with the standard deviation and the score percentages below and above the acceptable range (AR). RESULTS: The results demonstrated a substantial stability, with a gradual improvement, in dialytic adequacy, in anemic status and in PAS. The LVMI, calculated at the beginning and at the end of the period, did not demonstrate any significant changes. No significant changes were observed in the calcium-phosphorous metabolism parameters. Serum albumin and nPCR demonstrated the presence of malnutrition in 15-20% of patients. CONCLUSIONS: There was a more than adequate correlation between the target guidelines and that concerning the dialytic adequacy and the corrected anemic status. The improvement in parameters related to cardiovascular pathology, the risk of ectopic calcifications and malnutrition status, represented an achievable target.

[Determination of bone mineral content and correlations with calciotropic hormones in periodic hemodialysis patients]. / Determinazione del contenuto minerale osseo e correlazioni con gli ormoni calciotropi nei soggetti in emodialisi periodica.

The investigation on several forms of uremic osteodystrophy by means of bone mineral content (BMC) measurement led to contradictory conclusions. BMC in 27 patients on periodical hemodialysis treatment was measured correlating it to the seric levels of Ca, P, Mg, alkaline phosphatase (AP), calcitonin (Ct), osteocalcin (BGP), intact parathormone (PTHi), c-terminal and mean molecule PTH. Patients on dialysis treatment from a long period of time showed high AP and low BMC levels. This correlation proved significant just for the values recorded at a third distal site of radius. Patients with BMC under the normal range showed higher BGP levels and a longer period of dialytic treatment than those presenting normal BMC. The former showed a Ct inverse correlation as to age and mineralization indexes. Higher values of Ct and BMC have been reported in males rather than in females. Hence BMC is not suited to investigate different kinds of uremic osteodystrophy. Seric PTH dosage is certainly best fitted to discriminate patients affected with hyperparathyroidism from those with low turnover osteodystrophy. BMC determination is a valid support to evaluate the bone mineral loss in patients on haemodialysis treatment. It significatively correlates to the duration of the dialytic treatment; it is higher in female than in male population; it mainly affects cortical components rather than trabecular ones and is related to a seric Ct decrease.

Brain tumor death risk in mental patients.

Several investigators have previously reported a low cancer mortality in mental patients. They hypothesized there were possibilities of actual exclusion between cancer and psychosis. On the other hand, some Authors warned that the reported association between psychiatric illness and cancer death might vary, depending on the used statistical methods. To clarify this problem, we have examined the incidence of deaths caused by malignant neoplasm, particularly from brain tumor, in the chronic patients of Bisceglie Psychiatric Hospital, evaluating either absolute or relative mortality rate analysis. Our results seem to suggest an increased absolute mortality from malignant brain tumor in mental patients.