Normal spontaneous cortisol secretion in children after autologous bone marrow transplantation

AIM: To describe spontaneous cortisol secretion in children after autologous bone marrow transplantation (BMT) for acute leukaemia and lymphoma. METHODS: Spontaneous cortisol secretion was analysed in 39 children before and after BMT. Thirteen patients were conditioned with chemotherapy only (group 1), and 26 patients also with total body irradiation (TBI). In the TBI group, 14 patients had received no additional irradiation (group 2), whereas 12 patients had received cranial irradiation (CRT) previously (group 3). RESULTS: Before BMT, in comparison with group 1, mean morning cortisol was significantly lower in group 2 (252 vs 415 mmol/l, p = 0.004), but not in group 3 (vs 312 mmol/l, p = 0.12). There was no change in group 1 six months after BMT (to 379 nmol/l), whereas morning cortisol increased significantly in group 2 and group 3 (to 386 and 343 nmol/l, respectively; p < 0.05). The change in mean morning cortisol correlated negatively with pretransplant morning cortisol (r = -0.63, p < 0.001). Neither TBI nor CRT were associated with changes in morning cortisol. CONCLUSION: Spontaneous cortisol secretion is maintained after BMT irrespective of whether cranial or total body irradiation has been given or not.     

Differences in inhibition of replication between Coxsackie B4 virus strains in various cell lines by antibodies to some cell surface proteins

Monoclonal antibodies that interact with the decay accelerating factor (DAF, CD55), the lymphocyte homing receptor (CD44) or the intercellular adhesion molecule I (ICAM- 1) were found to inhibit the replication of different strains of Coxsackievirus serotype B4 (CBV-4) to various extent. By adding antibodies to CD55 the replication of two (V345 and VD2921) of seven strains in HeLa cells, three (V89-4557, VD2921 and T318) of seven in A549-10C cells and one (VD2921) of five strains in RD cells was blocked totally. Consequently, the replication of one strain (VD2921) was blocked in all cells indicating that this strain uses CD55 as a receptor or as a co-receptor on all cell lines and is unable to use another cell surface protein. The binding of this strain to the cell surface was inhibited by the antibodies to CD55. None of the CBV-4 strains was blocked totally by adding antibodies to CD44 to HeLa and A549-10C cells, whereas in RD cells the replication of one (T318) of the CBV-4 strains was blocked totally. The antibodies to ICAM-1 did not inhibit totally the replication of any strain in HeLa and RD cells, but it blocked totally the replication of one strain (CBV-4-E) in A549-10C cells. In HeLa and A549-10C cells the degree of replication correlated highly with the degree of cytopathic effect (CPE). In RD cells, four of the strains replicated without CPE. The adding of antibodies to the integrin alpha(v)beta(3) led to slightly enhanced replication of three of the CBV-4 strains in all cell lines. It is concluded that the receptor usage by different strains of CBV-4 varies not only within the same cells but also between different cell lines.     

Tissue culture of isolated human pancreatic islets infected with different strains of coxsackievirus B4: assessment of virus replication and effects on islet morphology and insulin release

The aim was to study whether different strains of Coxsackievirus B4 (CBV-4) are able to infect human pancreatic islet cells in vitro and cause morphological and functional damages. Isolated islets maintained in tissue culture were infected with five well- characterised strains of CBV-4. Aliquots of the culture medium were analysed with regard to virus replication and insulin content. Infected and uninfected islets were examined by light microscopy to determine the degree of virus-induced cytopathic effect (CPE). The results showed that the islet cells were susceptible to infection by all the strains of CBV-4 although the outcome of the infection differed. The virus titres obtained at 48 and 72 hours post infection differed significantly between all the CBV-4 strains (p<0.001), indicating different ability to replicate in islet cells. Pronounced to weak CPE, which was partly due to the origin (donor) of the islets, was induced by four of the five CBV-4 strains. One strain (VD2921) replicated without causing CPE despite high virus titres. One (V89-4557) of the CBV-4 strains always revealed pronounced CPE. Infection by this strain also caused functional impairment that significantly affected insulin response to high glucose at 48 hours post infection (p<0.001). Replication of another CBV-4 strain (JVB) in the islet cells significantly increased the release of insulin compared to non-infected control cells (p<0.001) indicating damage of the beta-cells leading to leakage of insulin.     

002 高血压及抗高血压药物与Ⅱ型糖尿病

本文采用前瞻性群体研究旨在确定降压药物的应用与继发Ⅱ型糖尿病的危险之间是否存在独立的相关性。 作者对12 550名(年龄45-64岁)无糖尿病的成年人进行全面健康评价(包括药物的使用及血压测定)。高血压判定标准为收缩压≥140mmH-g(1mmHg=0.1333 kPa)或舒张压≥90mmHg。确定高血压患者3 804例，根据使用降压药物的种类分为血管紧张素转化酶抑制剂(ACEI)162例，β阻滞剂543例，钙拮抗剂96例，噻嗪利尿剂458例，其它单一药物137例，多种药物(≥2种)934例，其余1 474例高血压患者未给予任何抗高血压药物治疗。随访3年及6年后，通过测定空腹血糖浓度[糖尿病判定标准为：空腹血糖≥126m/dl(≥7.0mmol/L)餐后血糖≥200m/dl(≥11.1mmol/L)]评价糖尿病新病例的发生率。     

Blood transfusion does not influence the development of malignant tumours.

OBJECTIVE: To investigate whether blood transfusion given to women during childbirth favours tumour development in later life. DESIGN: Retrospective cohort study. SETTING: County hospital, Sweden. SUBJECTS: 621 women who were given blood transfusions during childbirth compared with 1216 matched controls who were not given transfusions at the time of delivery. MAIN OUTCOME MEASURES: Overall and cancer-specific mortality, cancer morbidity, time interval between transfusion and diagnosis or death from cancer. RESULTS: After 21-31 years of follow-up of cancer morbidity and 22-32 years of overall and cancer-specific mortality, we found no significant differences between the groups. There were no differences in time from transfusion to diagnosis of malignant disease, or in time from transfusion to death from cancer. CONCLUSION: Blood transfusion given to women during childbirth does not promote malignant tumour development in later life, nor does it increase cancer mortality.     

Antiviral treatment of Coxsackie B virus infection in human pancreatic islets

Enterovirus infections of the pancreatic islets are believed to trigger or precipitate the near total destruction of beta-cells that constitutes type 1 diabetes (T1D). This study investigated the ability of an anti-picornaviral compound, pleconaril, to block the replication of two beta-cell tropic Coxsackie B4 virus (CBV-4) strains in isolated human islets. The two strains, VD2921 and V89 4557, with demonstrated abilities to cause non-lytic persistence or lytic infection, respectively, in islets, represented two different potential mechanisms behind virus-induced T1D. The virus replication in the islets was studied with and without addition of pleconaril. In addition, islet morphology was studied every day. To test the effects of pleconaril and/or DMSO on the beta-cells' insulin secretion, glucose perifusions were performed on treated and untreated islets. Virus titrations showed a clear reduction of the replication of both strains after pleconaril treatment. The VD2921 strain was inhibited to undetectable levels. The V89 4557 strain, however, showed an initial reduction of titers but virus titers then increased despite the addition of a second dose of pleconaril. This incomplete inhibition of viral replication suggested the existence of a resistant subtype within this strain. Pleconaril treatment reduced the beta-cells' insulin secretion in response to glucose stimulation in some experiments and induced slight morphological changes to the islets compared to untreated controls. In summary, pleconaril reduced the replication of the two beta-cell tropic CBV-4 strains in human islets. However, genetic differences between these strains influenced the effectiveness of pleconaril treatment. This stresses the importance of using multiple viral strains in antiviral tests.     

Long-term follow-up of acupuncture and hormone therapy on hot flushes in women with breast cancer: a prospective, randomized, controlled multicenter trial.

OBJECTIVE: To evaluate the effects of electro-acupuncture (EA) and hormone therapy (HT) on vasomotor symptoms in women with a history of breast cancer. METHODS: Forty-five women were randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months. The number of and distress caused by hot flushes were registered daily before, during and up to 24 months after start of treatment. RESULTS: In 19 women who completed 12 weeks of EA, the median number of hot flushes/24 h decreased from 9.6 (interquartile range (IQR) 6.6-9.9) at baseline to 4.3 (IQR 1.0-7.1) at 12 weeks of treatment (p < 0.001). At 12 months after start of treatment, 14 women with only the initial 12 weeks of EA had a median number of flushes/24 h of 4.9 (IQR 1.8-7.3), and at 24 months seven women with no other treatment than EA had 2.1 (IQR 1.6-2.8) flushes/24 h. Another five women had a decreased number of flushes after having additional EA. The 18 women with HT had a baseline median number of flushes/24 h of 6.6 (IQR 4.0-8.9), and 0.0 (IQR 0.0-1.6; p = 0.001) at 12 weeks. CONCLUSION: Electro-acupuncture is a possible treatment of vasomotor symptoms for women with breast cancer and should be further studied for this group of women.