Structuring a safer donor-replacement program

BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new- donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors.     

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

The use of ruthenium complexes as chemotherapeutic agents has been recently explored as one of the alternatives to conventional treatments. In the present study, two Ru(ii) polypyridyl complexes were synthesized and characterized: a strained [Ru(bipy)₂(BC)]Cl₂ (complex 1) where [bipy = 2,2′-bipyridine and BC = bathocuproine] along with the unstrained control [Ru(bipy)₂(phen)]Cl₂ (complex 2) where [phen = 1,10-phenanthroline]. The photophysical and photochemical analyses proved that unlike the photostable complex 2, complex 1 ejected both bipy and BC ligands at a ratio of 3 : 1 respectively. Results showed that the activity of complex 1 was significantly enhanced upon photoactivation. The response was however particularly significant in B16-F10 melanoma cells where phototoxicity index (PI = IC₅₀ dark/IC₅₀ light) was >900. When compared to cisplatin, the photoproducts were more potent against all tested cell lines, implying that the complex acquired significant chemotherapeutic potential upon irradiation. Cellular uptake of complex 1 and the free BC ligand were found to be significantly facilitated as evidenced by 400–600 fold increase in concentration of the compounds inside the cells relative to the extracellular culture medium. Complex 2 exhibited 35 times lower cellular concentration relative to complex 1. Flow cytometry and plasmid DNA gel electrophoresis measurements showed that complex 1 interacts with DNA inducing apoptosis in the dark and either late-apoptosis or necrosis upon irradiation. These findings corroborate the importance of lipophilic ligands such as BC to enhance uptake and subsequently improve the photochemotherapy potential of Ru(ii) polypyridyl complexes.

A strained Ru(ii) prodrug exhibited enhanced cellular uptake and phototoxicity due to its lipophilic properties.     

The effect of chemotherapy on the kinetics and proliferative capacity of normal and tumorous tissues in vivo

The proliferative state of a given tissue is a major determinant of its sensitivity to both phase-specific and cycle-specific chemotherapeutic agents. To study the extent of injury induced by antitumor agents to normal and tumorous tissues, a technique for following DNA synthesis as reflected in the incorporation of tritiated thymidine (3H-TdR) into DNA was compared to the conventional radioautographic technique of the labeling index (LI) and to the functional kinetic technique of granulocyte colony formation in vitro. Alterations in DNA synthesis induced by a single dose of cyclophosphamide in normal and tumorous tissues in vivo paralleled in many respects the changes seen when the more time-consuming techniques of the LI or granulocyte colony formation were employed. However, the recovery of granulocyte colony formation after cyclophosphamide therapy lagged behind the recovery of DNA synthesis in the bone marrow, obscuring a kinetic event of potential therapeutic significance. The determination of DNA synthesis simultaneously in normal and tumorous tissues in vivo was easy to perform and supplied therapeutically pertinent results comparatively quickly.     

A clonally distinct recurrence of Burkitt's lymphoma at 15 years

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.     

G蛋白偶联受体激酶的研究进展

G蛋白偶联受体激酶(GRKs)属丝氨酸／酪氨酸蛋白激酶家族,其亚型广泛存在于各种组织, 能特异地使活化的G蛋白偶联受体(GPCR)发生磷酸化及脱敏化,从而终止后者介导的信号转导通路．现就G蛋白偶联受体激酶的结构、种类及分布、生物学功能及与疾病关系的新进展进行总结与概括,并对其发展进行了展望．     

Mucosal vulval lichen planus: outcome, clinical and laboratory features

BACKGROUND: Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas. OBJECTIVE: To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features. SUBJECTS AND METHODS: Forty-four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected. RESULTS: Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC. CONCLUSIONS: Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long-term follow-up, and that all non-healing ulcerative and papular lesions should be biopsied.     

原位PCR技术及其应用

目的：阐述原位PCR技术的基本原理，进展，应用及存在问题。方法：通过检索国内，外相关文献，归纳整理，结合实践操作经验，展开分析，结果：原位PCR技术是一种特异性，敏感性较高的靶序列检测定位技术，作为研究基因信息和细胞，染色体等的形态信息的有力工具，尤其是专用原位PCR仪在医学研究（医学检验，病理学领域）上的广泛应用，结论：原位PCR技术的应用推广及研究深入，也存在其技术应用不完善之处。     

Experiences of special gynaecological services for children and adolescents: a descriptive study

Gynaecological examination of girls during childhood is undertaken somewhat infrequently. These genital examinations should not be taboo or a frightening experience for the girl, for her parents or for the physician. Studies of children suspected of sexual abuse have paid attention to the wide variety of gynaecological conditions already present in childhood. In 1988 we founded a special gynaecological outpatient clinic for girls under 16 y of age at a university hospital to develop the special knowledge and skills needed in children's gynaecology. In this gynaecological clinic for children and adolescents we were able to gain and offer expert knowledge of the problems of this age group. In this special clinic for children, gynaecological examination by special techniques and sonography led to a diagnosis in 71% of the patients without any instrumentation. Children and adolescent girls in need of special gynaecological care should be recognized specifically. Particular attention should be paid to the gynaecological care of victims of child sexual abuse and mentally or physically handicapped girls. In good co-operation with the girl, a gynaecological examination can become a positive experience during the development of female identity.