Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women.

PURPOSE: Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach. METHODS: This was a prospective, randomized, parallel group, open label, controlled versus no treatment clinical study. PCOS women aged > 18, free from systemic diseases and from pharmacological treatments were randomized with a 2:1 ratio for treatment with activated micronutrients in support to the carbon cycle (Impryl, Parthenogen, Switzerland-n = 22) or no treatment (n = 10) and followed-up for 3 months. Fasting blood homocysteine, AMH, testosterone, SHBGs, and the resulting FTI were tested before and at the end of the follow-up. RESULTS: The mean baseline fasting blood homocysteine was above the normal limit of 12 µMol/L and inversely correlated with SHBG. AMH was also increased, whereas testosterone, SHBG, and FTI were within the normal limit. The treatment achieved a significant reduction of homocysteine, that did not change in the control group, independently of the starting value. The treatment also caused an increase of AMH and a decrease of SHBGs only in the subgroup with a normal homocysteine at baseline. CONCLUSIONS: In PCOS ladies, blood homocysteine is increased and inversely correlated with the SHBGs. Physiologic amounts of activated micronutrients in support to the carbon cycle achieve a reduction virtually in all exposed patients. Whether this is of clinical benefit remains to be established.

Sequential vidarabine infusion in the treatment of polyoma virus-associated acute haemorrhagic cystitis late after allogeneic bone marrow transplantation.

Late onset haemorrhagic cystitis (HC) occurs in 20-30% of allogeneic bone marrow transplant patients. Human polyomavirus BK (BKV) (or less frequently adenovirus) may be involved in the pathogenesis of viral HC and can represent a serious post-transplant complication. Diagnosis and treatment of viral HC can be difficult and has an uncertain outcome. We report the efficacy of sequential vidarabine in the treatment of a patient with severe BKV-associated HC, despite the delay in implementing therapy. Bone Marrow Transplantation (2000) 25, 319-320.

Incidence of human cytomegalovirus infection in patients with refractory solid tumors receiving nonmyeloablative allogeneic stem cell transplants versus recipients of standard SCT for hematologic malignancies.

Human cytomegalovirus (HCMV) infection is the most frequent infectious complication after conventional allogeneic stem cell transplantation (alloSCT). From December 1998 to December 2002, we prospectively monitored HCMV reactivation in 59 patients affected by solid tumors and undergoing nonmyeloablative alloSCT (NST). Patients were allografted from HLA-identical sibling donors after fludarabine/cyclophosphamide-based conditioning regimens. Seventeen (28.8%) of 59 patients presented with HCMV antigenemia, and 14 received ganciclovir, with successful HCMV clearance in all cases. No patient developed HCMV viremia or disease. The median time to HCMV reactivation was 54 days (range, 16-245 days) after NST. These patients were compared with a cohort of hematologic patients who were treated with conventional myeloablative alloSCT. Matching criteria included HCMV risk group, stem cell source, donor type, and age. In the myeloablative group, HCMV active infection was observed in 47 (85.4%) of 55 patients at a median time of 30 days (range, 13-64 days) after alloSCT, and HCMV infection occurred more frequently ( P < .001) and earlier ( P = .001) than in NST patients. Patients affected with solid tumors undergoing NST had a reduced and delayed incidence of HCMV active infection.

Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors.

Several clinical observations have confirmed that a donor immune-mediated anti-malignancy effect, called graft-versus-leukemia or graft-versus-tumor, occurs following allogeneic hematopoietic stem cell transplantation. While the potential antitumor effect mediated by donor lymphocytes has been established in many hematological malignancies, its efficacy in inducing clinically meaningful responses in solid tumors has been largely unexplored despite evidence of its potential benefit in experimental animal models. Only in recent years has the investigational application of non-myeloablative stem cell transplantation in patients with refractory non-hematological cancers proved that a graft-versus-tumor effect can be generated in patients with metastatic renal cell cancer and possibly with other solid tumors. In the present article we review the biological basis, development and early clinical results of this novel immunotherapeutic approach for solid tumors.

Controversies in the management of brain metastases: the role of chemotherapy.

The role of chemotherapy (CT) for brain metastases (BrM) is still controversial. Limited life expectancy and presence of the blood-brain barrier (BBB) have been considered as contraindications for relatively aggressive therapies, such as CT. Nevertheless, more recent studies emphasise the possibility that in addition to historical nitrosoureas, also platinum derivatives, etoposide, teniposide, gemcitabine, irinotecan, topotecan and temozolomide can pass the BBB as they are active against selected BrM. Interaction of cytotoxic agents with other drugs may represent a problem in the treatment of BrM. By far, the most important factor conditioning the response to cytotoxic agents is the chemosensitivity of different tumours. CT proved to be effective in patients with BrM from lung cancer, mainly small cell lung cancer, breast cancer, choriocarcinoma and germ cell tumours. In these malignancies the responses to CT are similar to those observed in other metastatic sites. This observation, confirmed by many studies, contrasts with the theory, emphasised in the past, of the brain as a sanctuary. In fact BBB may be important in protecting normal brain tissue and micrometastases from CT, but not when BrM are symptomatic and clinically evident. The clue to the treatment of chemosensitive tumours is to assess the most active drugs and combinations. Cisplatin and etoposide was confirmed to be the treatment of choice in many situations (BrM from lung and also from breast cancer). Newer drugs are now on study: topotecan and temozolomide seem to be particularly promising (alone or in association with other drugs) in the treatment of various BrM (also from melanoma) and could represent an alternative to more widely-used drugs or as second-line treatments.

Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia.

BACKGROUND: The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. AIMS: To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. PATIENTS AND CONTROLS: Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p < 0.001). METHODS: Immunohistochemistry was performed on 3 microns sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine. RESULTS: The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (phi h value) was significantly higher in patients with CAG or ZES compared with controls (p < 0.01 in both patient groups versus controls). CONCLUSIONS: Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.