Long-term survival after vinblastine, bleomycin, and cisplatin treatment in patients with germ cell tumors of the ovary: An update

Thirteen patients with a malignant germ cell tumor of the ovary have been treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). In 12 patients a complete remission was reached, which was maintained in 10 of these patients. One patient with large tumor residues and a partial remission became CR after surgery. The tumor recurred in 2 patients after 6 and 27 months. Overall, 11 of these patients are in long-term remission, from 14 to 84 months after the start of treatment. VBP is an effective treatment for malignant germ cell tumors of the ovary, even in patients with large tumor residuals.     

Labially displaced ectopically erupting maxillary permanent canine: interceptive treatment and long-term results.

This case report demonstrates how extracting a maxillary deciduous canine affects the eruption path of a labially displaced ectopically erupting permanent canine. A long-term follow-up is presented, and the biologic mechanisms are discussed.     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Dipyridamole and RA-642 inhibit the production of superoxide anion and free radical damage to rat lens.

We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

Familial 46,XX gonadal dysgenesis

Two sisters, ages 18 and 25, presented with primary amenorrhea and underwent clinical, hormonal, cytogenetic, and pathologic evaluation. Both were of normal stature and lacking of somatic stigmata. Both patients had normal 46,XX karyotype on peripheral blood. Streak gonads were seen in both patients and a rather scanty number of primordial follicles was found in one patient. FSH, LH, and urinary estrogens were consistent with streak gonad syndrome. Autosomal recessive inheritance has been suggested in familial aggregates with XX gonadal dysgenesis.