Virus inactivation in red cell concentrates by photosensitization with phthalocyanines: protection of red cells but not of vesicular stomatitis virus with a water-soluble analogue of vitamin E

BACKGROUND: Photodynamic treatment of red cells (RBCs) with phthalocyanines and red light inactivates lipid-enveloped viruses, such as vesicular stomatitis virus (VSV) and human immunodeficiency virus. To protect RBCs from photodynamic damage, type I free radical quenchers, such as mannitol, which did not affect virus inactivation, were added. STUDY DESIGN AND METHODS: Aluminum phthalocyanine tetrasulfonate (AIPcS4) was found to inactivate VSV at a rate one- fourth that of the silicon phthalocyanines (Pc 4 and Pc 5). However, the latter also caused more RBC damage. To protect RBCs against this photodynamic damage, Trolox, a water-soluble vitamin E analogue, was used. RBC damage was measured as potassium leakage or hemolysis during storage after treatment. In addition, reduction in negative surface charge on RBCs was measured immediately after treatment, and the effect of Trolox on VSV inactivation in RBCs was evaluated. RESULTS: Trolox at a concentration of 5 mM was found to reduce potassium leakage during storage after Pc 4 and AIPcS4 photodynamic treatment of RBCs. Hemolysis during storage of RBC concentrates treated with Pc 4 or Pc 5 was drastically reduced by the addition of 5 mM Trolox prior to light exposure. At the same concentration, Trolox inhibited the reduction of negative surface charges on RBCs following Pc 4 and Pc 5 photodynamic treatment. Under these conditions, VSV inactivation by photodynamic treatment with all phthalocyanines was not affected by Trolox. In aqueous solution, Trolox formed a complex with AIPcS4, thus quenching the excited triplet state of AIPcS4 at a constant rate of 8.8 × 10(6) per M per second. CONCLUSION: These findings indicate that Trolox protects RBCs from phthalocyanine-photosensitized damage without affecting virus kill. The addition of Trolox would be beneficial for improving the quality of RBCs subjected to photodynamic treatment.     

IN SITU HYBRIDIZATION AND FLOW CYTOMETRIC ANALYSIS OF COLORECTAL TUMOURS SUGGESTS TWO ROUTES OF TUMOURIGENESIS CHARACTERIZED BY GAIN OF CHROMOSOME 7 OR LOSS OF CHROMOSOMES 17 AND 18

Chromosomal aberrations in colonic tumourigenesis were investigated by fluorescence in situ hybridization (FISH) with centromere-specific DNA probes and correlated to flow cytometry (FCM) results in a series of tissues including normal colonic epithelium, adenomas, and carcinomas, as well as adenomas adjacent to carcinomas. No numerical chromosome aberrations were detected in normal colonic epithelium, except for an extra chromosome X in one case. In the adenomas, the most frequently occurring chromosome aberration was a trisomy for chromosome 7, occurring in 37 per cent of the cases. In the carcinomas, two distinct routes of genetic aberration could be established on the basis of correlation with FCM: one with and one without endoreduplication. In the carcinomas without endoreduplication, trisomy or tetrasomy for chromosome 7 was detected in 12 out of 15 cases (80 per cent). In three of these cases, trisomy 7 was found in combination with loss of chromosome 17 and/or chromosome 18. In 87 per cent of the carcinomas with endoreduplication, loss of chromosome 17 and/or 18 was found, while in only one case was gain of chromosome 7 detected. In the adenomas adjacent to carcinomas, trisomy 7 was found in 36 per cent of the cases. In these cases, the concomitant adenocarcinomas showed the same numerical chromosome 7 aberration, plus extra aberrations for other chromosomes. In only two cases the carcinoma demonstrated trisomy 7 with a normal adjacent adenoma. These results suggest that gain of chromosome 7 is a significant aberration in the tumourigenesis of colonic carcinomas in which no endoreduplication has occurred. No marked clinico-pathological differences were observed between tumours of either route of tumourigenesis in this series.     

PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN

Twenty-four healthy women received 2·4 mg kg⁻¹ dolasetron mesylate (1·8 mg kg⁻¹ dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t_1/2=0·23 h) to MDL 74 156 (mean t_1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QT_c intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd.     

精液质量的正常参考值与男性生育能力

最近的研究表明:如果男性精液中精子密度低于40×106/mL,其生育能力就会随精子密度减少而相应下降。然而最新出版的《世界卫生组织人类精液分析实验室技术手册》第5版将正常精液密度的下限值,从原来的20×106/mL降低到15×106/mL。鉴于这一改动,全世界很大一部分生育能力低下的男性,将被认为"正常"而得不到适当的男科治疗。     

人内原性逆转录病毒基因表达及在染色体上的分布和功能与I型糖尿病的关系

目的 从病毒形态,基因表达,免疫,遗传及分子生物学角度来自四位新近发病的Ⅰ型糖尿病（ＩＤＤＭ）病人的胰腺等组织标本进行了研究。方法 从电子显微镜下观察糖尿病病人胰腺的ｂｅｔａ细胞胞浆中有Ｃ型病毒颗粒。从这些组织的互补ＤＮＡ基因库里检测内原性逆转录病毒ｐｏｌ基因的表达并分析研究它们的序列。结果 糖尿病病人组的ｐｏｌ基因表达与对照组相比有显著差异,特别是ＥＲＶ９,ＨＥＲＶ－Ｋ－ＭＬＮ,ＨＥＲＶＫ－Ｋ１     

Down-regulation of the Notch pathway mediated by a γ-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia

Background and purpose:

γ-Secretase inhibitors (GSIs) block NOTCH receptor cleavage and pathway activation and have been under clinical evaluation for the treatment of malignancies such as T-cell acute lymphoblastic leukaemia (T-ALL). The ability of GSIs to decrease T-ALL cell viability in vitro is a slow process requiring >8 days, however, such treatment durations are not well tolerated in vivo. Here we study GSI''s effect on tumour and normal cellular processes to optimize dosing regimens for anti-tumour efficacy.

Experimental approach:

Inhibition of the Notch pathway in mouse intestinal epithelium was used to evaluate the effect of GSIs and guide the design of dosing regimens for xenograft models. Serum Aβ₄₀ and Notch target gene modulation in tumours were used to evaluate the degree and duration of target inhibition. Pharmacokinetic and pharmacodynamic correlations with biochemical, immunohistochemical and profiling data were used to demonstrate GSI mechanism of action in xenograft tumours.

Key results:

Three days of >70% Notch pathway inhibition was sufficient to provide an anti-tumour effect and was well tolerated. GSI-induced conversion of mouse epithelial cells to a secretory lineage was time- and dose-dependent. Anti-tumour efficacy was associated with cell cycle arrest and apoptosis that was in part due to Notch-dependent regulation of mitochondrial homeostasis.

Conclusions and implications:

Intermittent but potent inhibition of Notch signalling is sufficient for anti-tumour efficacy in these T-ALL models. These findings provide support for the use of GSI in Notch-dependent malignancies and that clinical benefits may be derived from transient but potent inhibition of Notch.     

Latex allergy in children: modalities and prevention

Allergic or immediate hypersensitivity reactions to latex have been reported in children with increasing frequency in the past. The reported prevalence varies greatly depending upon the population studied and the methods used to detect sensitization. Children's subpopulations at particular risk include: atopics, individuals with spina bifida, children undergoing surgical procedure during the neonatal period and individuals who required frequent surgical instrumentations. Latex allergy is also an important medical issue, particularly for healthcare personnel. Sensitization mainly occurs by wound or mucosal contact with latex devices during surgery or by inhalation of airborne allergens released from powdered latex gloves. Regarding diagnosis, the medical history, skin prick test and search for specific serum IgE are crucial but cost effective. The development of a guide listing latex-containing drugs is essential for the primary prevention of allergic reactions. Immunotherapy or specific premedication seems not effective in preventing the risk of anaphylaxis during the perioperative course. The most effective strategy to decrease the incidence of latex sensitization is complete avoidance. This strategy is efficient in patients and also in health care workers and has been applied since 2002 in our pediatric surgical hospital. One of major problem with the latex-free gloves was that surgeons find them considerably more difficult to work with. But today, manufacturers made considerable effort and free-latex gloves with an equal tactile sensation than the latex-gloves are now available. The extra cost of free latex gloves is well counterbalanced as allergen test, long stay hospital for allergic reaction, and worker's compensation are no longer needed. Since the introduction of this program in our institution, no allergic reaction to latex has been reported in 25000 anesthetized children or with the health care workers.     

少数民族患者对门诊服务需求的调查分析

目的 了解少数民族患者在门诊分诊过程中的服务需求,分析其存在的相关影响因素,探讨如何提高门诊护士与少数民族患者的沟通效果.方法 运用自行设计问卷对145名少数民族患者进行调查,并对其结果进行分析.结果 少数民族患者在门诊分诊服务中,认为最为重要的需求是对护士素质的提高,其得分为(33.99±4.13)分,其次是对就医环境的需求程度相对较高.结论 应加强门诊分诊服务水平及质量,满足少数民族患者的就医需求,提高门诊少数民族患者的满意度.     

Diagnosis and treatment of pyogenic bone infections

Background

Pyogenic osteomyelitis is still frequently seen in the developing world and the treatment of chronic osteomyelitis presents a considerable challenge despite advances in microbiological techniques, antibiotics and surgical techniques. Acute haematogenous osteomyelitis is commoner in children.

Results

In the pre-antibiotic era, mortality rate was high and progression to chronic osteomyelitis was common. A near similar scenario still exists in many developing countries due to the combination of inappropriate and/or inadequate antibiotic therapy, delayed presentation and unorthodox interventions by traditional healers.

Discussion

Chronic osteomyelitis may result from poorly treated or untreated acute osteomyelitis, open fractures, surgery for an array of orthopaedic conditions and from contiguous spread from infected soft tissue as may occur in diabetic foot infections. A large array of treatment techniques hinged on sequestrectomy/ debridement, management of dead space, improvement of oxygenation and perfusion to ischaemic tissue exist. Despite these, total eradication of disease is difficult.

Conclusion

This article summarizes the pathology and methods of management available for pyogenic osteomyelitis. In its acute and chronic forms, the disease is likely to remain prevalent in the developing world until issues of ignorance, poverty and prompt access to appropriate and efficacious medical care are addressed.