High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow- up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.     

Antitrypanosomal potentials of the extract and fractions of Abrus precatorius seeds

ObjectiveTo evaluate the in vivo trypanocidal activity of the methanol extract and fractions of Abrus precatorius seeds in mice.MethodsParasiteamia was induced unto mice by intraperitoneal injection of 1.25×10⁵ Trypanosoma in normal saline. Five days when a high level of parasiteamia was established treatment commenced until ten days. The mice were treated with 10, 20 and 40 mg/kg bt. of the extract and 5 and 10 mg/kg bt. of the fraction (F₂), respectively for 5 days. Diminazene aceturate at the dose of 3.5 mg/kg bt. for two days was used as the reference drug. The level of parasitaemia and packed cell volume (PCV) of the animals estimated.ResultsAt doses of 10, 20 and 40 mg/kg the crude extract showed a sharp reduction in the level of parasitaemia in mice compared with the untreated group. The mice treated with F₂ at doses of 5 and 10 mg/kg showed a sharp reduction in the level of parasitamia to zero in day 9, and a gradual recovery from the 12th day of treatment. This effect is comparable to that of the mice treated with 7 mg/kg of standard drug diminazene aceturate. The PCV of the treated showed a gradual decrease with time, but not as much as the untreated group. Phytochemical screening revealed the presence of glycosides, alkaloids, carbohydrates, tannins and proteins in the Abrus precatorius powder while F₂ was rich in alkaloids.ConclusionsThis study shows that both the extract and the fractions of Abrus precatorius seeds exhibited a promising trypanocidal property. Alkaloids may be responsible for the observed activity.     

Experience with a transfusion recipient education program about hepatitis C

Shortly after test kits for antibodies to the hepatitis C virus (HCV) were licensed in May of 1990, our medical community undertook a public education program encouraging previous transfusion recipients to see their physicians about the wisdom of being tested for anti-HCV. In response, 1034 samples were received for testing. All samples repeatably reactive (RR) with anti-HCV enzyme-linked immunoassay (EIA) were tested further with a research recombinant immunoblot assay (RIBA). Overall, 76 of the 1034 (7.4%) recipient samples were RR and 64 of these (84.2%) were reactive with RIBA. Recipients transfused prior to surrogate testing (alanine aminotransferase [ALT] and anti-hepatitis B core [anti-HBc]) in 1986 showed a 8.6 percent reactivity with RIBA and those transfused after surrogate testing showed a 4.8 percent reactivity, a 44 percent reduction. Of the 57 recipient samples reactive with RIBA and suitable for assay, 11 (19.3%) had an elevated ALT. Among 76 randomly selected blood donors with RR EIAs studied for comparison with recipients, 20 (26.3%) were reactive with RIBA, 9 of which had an abnormal surrogate test that would have disqualified them. ALT concentrations were abnormal in 6 (30%) of the donors who were reactive on RIBA. We conclude that an education program that encourages previous transfusion recipients to seek medical advice about anti-HCV testing is practical from the standpoint of the blood center. We believe more widespread implementation of similar programs should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microstructural assessment of rare corneal dystrophies using real-time in vivo confocal microscopy

Purpose : To analyse and describe three cases of rare corneal dystrophy and highlight their in vivo microstructural features. Methods : Subject 1 was diagnosed with a posterior stromal fleck corneal dystrophy. Two of her three children were also affected. Subjects 2 and 3 exhibited an almost identical clinical appearance on biomicroscopic examination, such that both clinically were diagnosed as having pre‐Descemet’s dystrophies. All subjects underwent in vivo confocal microscopy and approximately 300 sequential digital images were obtained and analysed for each cornea. Results : In vivo confocal microscopy of subject 1 demonstrated an abnormal appearance of numerous large ovoid particles, measuring 50–70 μm in diameter in the mid and posterior stroma as well as smaller hyperreflective dot‐like intracellular deposits, of less than 1 μm diameter. Despite the near‐identical clinical appearance, subjects 2 and 3 could be clearly differentiated by in vivo confocal microscopy. Subject 2 exhibited small, irregular, optically dense particles, mainly in the anterior stroma, whereas subject 3 possessed classical involvement of the stroma immediately adjacent to Descemet’s membrane, with numerous regular, small, hyperreflective particles. Conclusions : The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers may help to resolve whether abnormalities are intra‐ or extracellular, and aid clearer differentiation of rare corneal disorders.     

Treatment of herpes zoster related corneal neovascularisation and lipid keratopathy by photodynamic therapy

Traditionally, photodynamic therapy (PDT) has been used to treat choroidal neovascularisation. More recently, its use in corneal neovascularisation has provided promising clinical results. The major advantage of PDT is that it is minimally invasive, resulting in closure of the neovascular network without damaging the surrounding healthy tissue. This report describes the positive results of PDT, clinically and microstructurally, as imaged by in vivo confocal microscopy, for treating corneal neovascularisation with lipid keratopathy, secondary to herpes zoster infection.     

Estimation of aneuploidy for chromosomes 3, 7, 16, X and Y in spermatozoa from 10 normospermic men using fluorescence in-situ hybridization

Fluorescence in-situ hybridization (FISH) is a fast and efficient method of estimating aneuploidy in human spermatozoa. In this study, we have estimated baseline disomy frequencies in spermatozoa from a group of 10 normospermic men, using stringent scoring criteria. A triple- probe FISH procedure was used for chromosomes 3, X and Y, while a double-probe FISH method was used for chromosomes 7 and 16. A total of 101273 spermatozoa were scored for chromosomes 3, X and Y, resulting in 97.83% haploidy (3X or 3Y), 0.39% disomy (33X, 33Y, 3XX, 3YY or 3XY) and 0.35% diploidy (33XX, 33YY or 33XY). A total of 100760 spermatozoa were scored for chromosomes 7 and 16, giving 98.9% haploidy (716), 0.11% disomy (7716 or 71616) and 0.27% diploidy (771616). Disomy frequencies for individual chromosomes differed (chromosome 3, 0.20%; chromosome 7, 0.05%, chromosome 16, 0.06%; X + Y, 0.19%). The frequency of disomy 3 was significantly higher than disomy 7 (P = 0.019) and disomy 16 (P = 0.022), while the frequency of sex chromosome disomy was significantly higher than disomy 7 (P = 0.0058) and disomy 16 (P = 0.0067), but not disomy 3 (P = 0.73). The disomy and diploidy (0.27- 0.35%) estimates obtained for this normospermic population were generally low and were similar to other recent reports.