艾滋病合并隐球菌脑膜炎18例临床分析

目的　提高对艾滋病 (AIDS)合并隐球菌脑膜炎的认识。方法　对赤道几内亚巴塔地区医院 18例AIDS合并隐球菌脑膜炎患者进行临床综合分析。结果　 18例AIDS合并隐球菌脑膜炎患者的临床主要表现为 :发热、剧烈头痛、极度乏力、肢体痛、脑膜刺激征及消瘦与脱水等。脑脊液 (CSF)培养均为新型隐球菌生长 ;涂片及隐球菌多糖荚膜抗原 (ELISA法 )检测的阳性率分别为 77 8% (14/ 18) ,94 4% (17/ 18)。结论　隐球菌脑膜炎为AIDS常见机会性感染及主要致死病因之一。     

Balancing high accrual and ethical recruitment in paediatric oncology: a qualitative study of the 'look and feel' of clinical trial discussions

Background  

High accrual to clinical trials enables new treatment strategies to be tested rapidly, accurately and with generalisability. Ethical standards also must be high so that participation is voluntary and informed. However, this can be difficult to achieve in trials with complex designs and in those which are closely embedded in clinical practice. Optimal recruitment requires a balance of both ethical and accrual considerations. In the context of a trial of stratified treatments for children with acute lymphoblastic leukaemia (UKALL2003) we examined how recruitment looked to an observer and how it felt to the parents, to identify how doctors' communication could promote or inhibit optimal recruitment.     

Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1- ¹³C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3–17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean ±SEM: 250 ±28 and 228 ±22 μg l^-1, respectively). During FN, IGF-I fell to 156 ±22 /ng l ^-1(p= 0:02), and rose to 276 ±27 μ g l ^-1 with recovery at 6 months (p = 0:004). Similarly, IGFBP-3 decreased from 4.0 ±0.2mgl^-1 before chemotherapy to 3.0 ±0.3 mgl^-1 during FN (p= 0:01), and returned to 4.1 ±0.2mgl ^-1 at 6 months (p= 0:01). IGF-I correlated with IGFBP-3 (r=+0:7, p <0:001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6 ±3.5 to 30.6 ±2.8/ngl^-1 (p = 0:004), whereas serum insulin decreased from 26.5 ±6.8 to 7.8 ±0.8 mUl^-1 (p= 0:03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3 ±0.6 to 6.7±0.8mUl ^-1 (p= 0:01), and cortisol from 197 ±48 to 594±98nmoll ^-1 (p = 0:005). Albumin decreased from 47 ±2 to 38 ±2gl^-1 (p= 0:004) and improved to 47 ±2gl^-1 with recovery (p= 0:003). Protein synthesis increased from 4.5 ±0.4 to 5.0 ±0.6gkg^-1 d^-1 before chemotherapy and during FN, while protein breakdown rose from 5.4 ±0.4 to 6.3 ±0.4kg^-1d^-1. Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.     

Spinal cord compression–do we miss it?

Four children with spinal cord compression due to malignant tumours are presented. The severity of the condition was not initially recognized by parents, or the nature of the likely cause by the initial physicians. Lower limb asymmetrical weakness, clear-cut sensory levels, and marked pain indicate need for urgent imaging and exclusion of a space occupying lesion. In 1997 diagnosis of Guillain-Barré syndrome should not be made without careful prior spinal imaging.     

HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful cervical cerclage

The release of certain cytokines, e.g. tumour necrosis factor (TNF)- alpha, in the amniotic fluid has been suggested to be a cause of preterm birth. The predisposition to excessive liberation of cytokines from peripheral leukocytes has been shown to depend partly on the individual's HLA-DR genotype. The HLA-DR1 and -DR3 alleles have previously been reported as being associated with a TNF-alpha high responder status and have also been associated with unexplained recurrent spontaneous abortions. In the present study, HLA-DR typing was performed in 10 women who had experienced recurrent very early preterm births resulting in perinatal death, or late spontaneous abortions under a clinical picture resembling that traditionally attributed to cervical incompetence. All patients had had at least one mid-trimester miscarriage in spite of the insertion of a cervical cerclage. Nine out of 10 (90%) patients had the HLA-DR phenotypes DR1 and/or DR3 compared with 37% in the background population (P < 0.005). The results suggest that HLA-DR-associated immunological factors might play a part in recurrent late spontaneous abortions and extremely preterm births under a cervical incompetence-like picture, at least in the subset of cases not treatable by cervical cerclage.      

Dental health in children with cancer

This study investigated the dental health of children (aged 1-14 years) diagnosed with cancer 4-36 months earlier. Sixty patients were examined and interviewed; 43% had untreated decay and only 35% had seen a dentist since their malignancy had been diagnosed. A significant source of bacterial infection is not being treated in this at risk population. The level of dental disease and lack of dental prevention indicates a need to integrate medical and dental care.     

Inhibitors of catechol-O-methyltransferase sensitize mice to pain

BACKGROUND AND PURPOSE

Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson''s disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodynia and hyperalgesia in a model of diabetic neuropathy. Here, we have assessed the effects of acute and repeated administrations of COMT inhibitors on mechanical, thermal and carrageenan-induced nociception in male mice.

EXPERIMENTAL APPROACH

We used single and repeated administration of a peripherally restricted, short-acting (nitecapone) and also a centrally acting (3,5-dinitrocatechol, OR-486) COMT inhibitor. We also tested CGP 28014, an indirect inhibitor of COMT enzyme. Effects of OR-486 on thermal nociception were also studied in COMT deficient mice. Effects on spinal pathways were assessed in rats given intrathecal nitecapone.

KEY RESULTS

After single administration, both nitecapone and OR-486 reduced mechanical nociceptive thresholds and thermal nociceptive latencies (hot plate test) at 2 and 3 h, regardless of their brain penetration. These effects were still present after chronic treatment with COMT inhibitors for 5 days. Intraplantar injection of carrageenan reduced nociceptive latencies and both COMT inhibitors potentiated this reduction without modifying inflammation. CGP 28014 shortened paw flick latencies. OR-486 did not modify hot plate times in Comt gene deficient mice. Intrathecal nitecapone modified neither thermal nor mechanical nociception.

CONCLUSIONS AND IMPLICATIONS

Pro-nociceptive effects of COMT inhibitors were confirmed. The pro-nociceptive effects were primarily mediated via mechanisms acting outside the brain and spinal cord. COMT protein was required for these actions.