Brain metastases as isolated site of relapse in patients with epithelial ovarian cancer previously treated with platinum and paclitaxel-based chemotherapy

Brain metastases in patients with epithelial ovarian cancer (EOC) have an estimated incidence of 0.3-1.9% and are isolated in up to 50% of these patients. The risk factors and the prognostic significance of isolated central nervous system (CNS) relapse in patients with EOC who received primary treatment with platinum and paclitaxel have not been identified. We conducted a retrospective study in patients with EOC who relapsed with isolated brain metastases and report our experience. Two hundred sixty-seven patients with stages III and IV EOC, in clinical complete remission after first-line treatment with platinum and paclitaxel, were included in our analysis. After a median follow-up of 65 months, 150 patients had relapsed. Eight patients (5%) had isolated brain metastases. Patient and disease characteristics did not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS. Median time to first disease relapse, overall survival, and survival after relapse did not differ significantly between patients with brain metastases and those with relapse outside the CNS. Two patients have died 6 and 12 months after the diagnosis of brain metastases, and 5 patients are alive 4-35 months after the diagnosis of isolated brain metastases. Three patients remain free of disease 4-18 months after treatment with radiotherapy and systemic chemotherapy for their CNS metastatic disease. Patients with isolated brain metastases have comparable survival to patients with relapse outside the CNS, and long-term remission can be achieved in some cases, provided that systemic chemotherapy is added to local treatment.     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

Complications of Preservatives in Contact Lens Solutions

ABSTRACT The addition of preservatives in contact lens solutions has been used as a means of killing bacteria or preventing their growth. With the widespread use of preservatives it has become increasingly evident that they have the ability of being adsorbed and absorbed by contact lenses. Consequently, the ocular tissues can be exposed to preservatives over a prolonged period of time. Since the 1970s practitioners have become aware of the adverse reactions resulting from the use of preservatives. The frequency of the complications attributed to the use of preservatives is difficult to ascertain, but most manufacturers and practitioners estimate it to be in the victinity of 5–10%. Preservatives have been shown to have a toxic effect on the cornea, causing disruption of cell structure and possible malfunction of epithelium, stroma and endothelium. In recent years preservatives, in particular thimerosal, have been recognized as having the ability to elicit allergic responses. This paper reviews the present literature on the complications of using preservatives. It concludes that much more research is needed in this area. Until the long term implications of preservatives in contact lens solutions are known, heat disinfection with non-preserved saline is a practical and safer alternative.     

Macrophages and HLA-DR(+) cells in acutely rejecting kidney transplants, predict subsequent graft survival, even after reversal of the acute episode

Renal graft biopsies from 19 selected patients with acute cellular rejection (ACR) were analysed using a panel of monoclonal antibodies. All patients had only one episode of ACR, which was completely reversible. In 11 patients (group 1) graft function slowly deteriorated over a period of 14 (±17) months after the episode. In the remaining eight (group 2) graft function remained stable over a similar period of observation. In group 1 there was a significantly increased inflitrate of glomerular and interstitial monocytes/macrophages (MM) when compared with group 2. Also, the expression of HLA-DR antigen by the tubular cells were stronger in group 1, while T-cells in the glomeruli and the interstitium were equally distributed in both groups. We conclude that large numbers of MM and HLA-DR expressing cells (glomerular, interstitial and tubular) in rejecting kidneys predict a more rapid decline of follow-up renal function despite reversal of the acute episode. This may suggest that subclinical ongoing injury continues in some patients and perhaps more intense immunosuppression is necessary to prevent graft loss.     

Has Gallo proven the role of HIV in AIDS?

The evidence that Robert Gallo and his colleagues presented on 4th May 1984 regarding HTLV-III (HIV) isolation and the role of HIV in the pathogenesis of AIDS is critically analysed. It is concluded that the evidence does not constitute proof of the isolation of a retrovirus, that the virus is exogenous, or that the virus is causally related to AIDS.     

Reduced density and morphologic alteration of Ia and ADPase positive Langerhans cells after low-protein diet

This study examined the effects of low-protein diet on the population density, morphology and histochemical characteristics of Langerhans cells. Weaned at 18 days old, BALB/c mice were divided into two groups: one group received a high-protein diet (20% casein) and the other was fed an isocaloric low-protein diet (caesin 4%). After 14 days, the mice were killed and the skin of the ears was removed for investigation. Langerhans cells were visualized using ADPase and anti-Ia immunoperoxidase techniques. In protein malnourished mice, the density of ADPase and Ia-positive Langerhans cells was significantly reduced, while morphometric assessment of their cross-sectional area showed a significant reduction of total cell area, cell body area and degree of arborization. Quantitative cytophotometric analysis revealed a reduction of ADPase ectoenzyme activity and decreased concentration of membrane Ia antigen. We postulate that these changes affect Langerhans cell functions, and in turn influence the immune mechanisms in the skin.     

The Genetic Background Modulates the Effect of the Beige Gene on Susceptibility to Cytomegalovirus Infection in Mice

Homozygous beige (bg/bg) mice were more susceptible to the development of fatal disease induced by murine cytomegalovirus (MCMV) than their bg/ + littermates. However, the increase in susceptibility depended on the genetic background of the strain carrying the bg gene. C57BL/6, SB/Le, DBA/2, and CBA bg/bg mice showed, respectively, 2.5-, 3.2-, 9.5-, and 18.6-fold increases in susceptibility compared with the corresponding bg/+ animals. Beige mice showed higher liver titres of MCMV than bg/ + by the 2nd or 3rd day after infection, and tissue damage was also greater. Splenic NK cells were not detected in uninfected bg/bg mice, and after virus inoculation the increment in cytotoxicity was greater in bg/ + than in bg/bg mice. However, cytotoxicity towards WEHI-164 cells was not impaired in bg/bg mice and was not augmented by MCMV. Interferon titres were also not impaired by the beige mutation. Of the strains examined, CBA had the highest endogenous levels of NK cells and were most genetically resistant to MCMV. Thus, our observation that the beige gene had the greatest effect on susceptibility in this strain suggests that NK cells are important mediators of genetically determined resistance to MCMV.