辣椒素受体介导氯喹引起的搔痒

目的研究辣椒素受体（VR1）在氯喹引起搔痒中的作用及机制。方法实验分4个部分,分别研究辣椒素受体拮抗剂辣椒平腹腔注射、局部应用辣椒素使VR1脱敏感、局部注射PKA抑制剂H89或PKC抑制剂bisindolylmaleimide Ⅰ、重复肥大细胞脱颗粒后颈背部注射氯喹200μg／100μl 30min内引起搔痒的次数,分为9小组,共使用6周龄C57BL／6J雄性小鼠63只。结果腹腔内注射辣椒平、局部应用辣椒素与重复肥大细胞脱颗粒均明显抑制氯喹引起的搔痒,而H89与BIM对氯喹引起的搔痒均无明显作用。结论氯喹通过肥大细胞脱颗粒引起搔痒,而辣椒素受体介导了氯喹引起的搔痒。     

A randomized,placebo-controlled,double-blind trial of ondansetron in renal itch

BACKGROUND: Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Ondansetron, a serotonin type 3 receptor antagonist was developed for relief of chemotherapy induced nausea. Recently, anecdotal reports describe relief of renal itch with ondansetron. OBJECTIVES: We performed a double-blind randomized placebo-controlled trial to objectively assess the effectiveness of ondansetron in renal itch. PATIENTS AND METHODS: With approval from the local ethical committee, 24 patients on haemodialysis were enrolled in the trial. On a random basis 14 patients were blindly allocated to the ondansetron-placebo sequence and 10 to the placebo-ondansetron sequence. Baseline values for itch were obtained for 7 days before the treatment period and there was a 7-day washout between the treatment periods. During the treatment patients received either 8 mg of ondansetron three times a day or a placebo tablet three times a day for 2 weeks. Patients were asked to record the severity of their pruritus on a visual analogue scale (VAS) twice a day. At the end of the study patients were asked blindly which treatment they had preferred. RESULTS: Seventeen patients completed the trial. Pruritus decreased by 16% (95% CI: 0.5-32%) during active treatment and by 25% (95% CI: 9-41%) during treatment with placebo. The change in VAS scores during treatment with ondansetron (P = 0.04) and placebo (P = 0.01) were both significant. Eleven patients expressed a preference, seven for placebo and four for ondansetron. CONCLUSIONS: Our results show that ondansetron is no better than placebo in controlling renal itch.     

Cutaneous response to irritants

We evaluated the role of pre-existing dermatitis in the response to irritants by patch testing the skin of 40 healthy volunteers and the uninvolved skin of 480 subjects for 2 days. These latter were affected by active atopic dermatitis, psoriasis, eczema with positive and negative patch test reactions, urticaria and generalized pruritus. A first panel containing 15 micro L of aq. solutions of disodium laureth sulfosuccinate (NaLSS) 5% and 10%, potassium cocoate (KCC) 5%, potassium oleate (KOL) 5%, zinc coleth sulphate (ZnCS) 5%, sodium mireth sulphate (NaMS) 5%, sodium cocoamphoacetate (NaCCAA) 3% and 5%, was simultaneously applied to 1 site on the upper back. The results, scored by visual assessment, were compared to those observed when testing on the opposite side a second panel containing 15 micro L of aq. solutions of 3 well-known irritants, benzalkonium chloride (BAK) 1%, sodium lauryl sulphate (SLS) 1%, and dimethylsulphoxide (DMSO) 10%. Whilst the substances of the first panel and DMSO gave, on the whole, a scarce number of positive responses in all the tested groups, more evident differences in number, percent and mean intensity of the positive responses to BAK and SLS were found between the different groups. Although some of them seemed statistically significant, when the same values were evaluated by means of chi2 and Student t-test, they did not differ in a statistically significant way from the values found in healthy subjects. The results of this study seem to indicate that the substances of the first panel have a chemical structure that makes them quite safe in real-life conditions. In contrast, BAK and SLS have chemical properties that condition the number and intensity of the responses, making the role exerted by the pre-existing dermatosis quite marginal. In particular, there is no proof that the healthy skin of active atopic subjects is the most susceptible to the irritating effects of the tested substances.     

Thalidomide in the management of epidermolysis bullosa pruriginosa

Epidermolysis bullosa (EB) pruriginosa is a distinctive clinical subtype of dystrophic EB. We report a patient with dominant dystrophic EB pruriginosa, who had an excellent response to systemic thalidomide treatment. The mechanism of action of thalidomide in the management of pruriginous disorders is not yet completely understood. Most recent studies point towards an immunomodulatory action of thalidomide that may suppress excessive production of tumour necrosis factor-alpha and may downregulate certain cell surface adhesion molecules involved in leucocyte migration.     

Familial brachioradial pruritus

BACKGROUND: The cause of brachioradial pruritus (a localized itching on the arms or shoulders) is controversial. A hereditary form of this condition has not been reported. OBJECTIVES: To describe the occurrence of brachioradial pruritus in several members of one family. PATIENTS AND METHODS: The pedigree of the three generations and the history of brachioradial pruritus was outlined. Four sisters were investigated by radiography of the cervical spine. RESULTS: Five sisters and one brother, together with five of their daughters suffered from recurring brachioradial pruritus. The sisters had had occupations requiring heavy lifting, spent much time outdoors and exposed themselves extensively to the sun. Several complained of neck pain and cervical radiographs of four of them indicated arthrosis. CONCLUSIONS: Spinal disease alone cannot explain the symptoms of brachioradial pruritus, which in our patients was characterized by symptom-free periods broken off by relapse late in the summer each year. The pedigree suggests this hereditary form of brachioradial pruritus to be dominant and possibly X-linked.     

Incapacitating lower limb pain syndrome in cord blood stem cell transplant recipients with calcineurin inhibitor

Calcineurin-inhibitor induced pain syndrome (CIPS) is a newly described entity with a characteristic feature of sudden onset of severe lower limb pain, and high levels of cyclosporine or tacrolimus may be involved in the pathogenesis. This syndrome is rarely seen in recipients of hematopoietic stem cell transplantation (HSCT) compared with other organ transplant recipients, however, heightened awareness of this complication after HSCT may be needed for hematologists, as misdiagnosis can result in catastrophic consequences. We report herein two cases of lower limb pain syndrome, with some clinical features resembling CIPS, occurring during the early phase of cord blood stem cell transplantation for hematological malignancy.     

The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine,fentanyl and adrenaline after major surgery. A randomized,double-blind,dose-finding study

BACKGROUND: We have documented that adrenaline 2.0 micro g.ml- 1 markedly improves relief of dynamic pain when added to a thoracic epidural analgesic infusion of bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1. Concern about possible adverse effects on spinal cord blood flow, expressed by others, prompted us to find the lowest concentration of adrenaline needed to produce effective and reliable pain relief after major surgery. METHODS: A prospective, randomized, double-blind, parallel group study was carried out in 36 patients after major thoracic or upper abdominal surgery. Patients with only mild pain when coughing during titrated thoracic epidural infusion of approximately 9 ml per hour of bupivacaine 1 mg.ml- 1, fentanyl 2 micro g.ml- 1, and adrenaline 2.0 micro g.ml- 1 were included. The study was conducted as a dose-finding study comparing three different adrenaline concentrations in the epidural mixture (0.5, 1.0, and 1.5 micro g.ml- 1) with each other and with adrenaline 2.0 micro g.ml- 1 in our standard epidural mixture. On the 1st postoperative day, the patients were randomly allocated into three equal groups of 12 patients each, and given a double-blind epidural infusion at the same rate, but with different adrenaline concentrations (0.5, 1.0, or 1.5 micro g.ml- 1). The effects were observed for 4 h or until pain when coughing became unacceptable in spite of rescue analgesia. Rescue analgesia consisted of up to two patient-controlled epidural bolus injections per hour (4 ml) and subsequent i.v. morphine, if necessary. All patients received rectal paracetamol 1 g, every 6th hour. Main outcome measures were pain intensity at rest and when coughing, evaluated by a visual analogue scale and an overall quality of pain relief score. The extent of sensory blockade was evaluated by determining dermatomal hypaesthesia to cold. RESULTS: Pain intensity when coughing increased (P < 0.001) and the number of hypaesthetic dermatomal segments decreased (P < 0.002) when the concentration of adrenaline was reduced below 1.5 micro g.ml- 1 in the triple epidural mixture. This change started within two hours after reducing the concentration of adrenaline below 1.5 micro g.ml- 1. The differences in pain intensities at rest were less pronounced. After 4 h with adrenaline 0.5 or 1.0 micro g.ml- 1 pain intensity when coughing was unacceptable in spite of rescue analgesia. After restarting the standard epidural mixture with adrenaline 2.0 micro g.ml- 1, pain intensity was again reduced to mild pain when coughing and the sensory blockade was restored. Occurrence of pruritus increased with a decreasing adrenaline concentration. CONCLUSIONS: Adrenaline in a dose-related manner improves the pain-relieving effect and sensory blockade and decreases the occurrence of pruritus of a low-concentration thoracic epidural analgesic infusion of bupivacaine 1 mg. ml- 1 and fentanyl 2 micro g.ml- 1 after major thoracic or upper abdominal surgery. The minimally effective concentration of adrenaline, when added to bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1, to maintain relief of dynamic pain is approximately 1.5 micro g.ml- 1. The data clearly document that dynamic, cough-provoked pain is a more sensitive outcome measure for postoperative pain relief than pain at rest.     

Generic and disease-specific health related quality of life of liver patients with various aetiologies: A survey

Most studies on health related quality of life (HRQoL) of chronic liver patients were done in small clinical populations or restricted to one aetiology or disease stage. There is still a need for a study in a large liver patient population with various aetiologies and disease stages, approaching a population-based study. We evaluated the impact of liver disease aetiology on generic HRQoL, disease-specific HRQoL and fatigue and we compared HRQoL and fatigue between aetiological groups and healthy Dutch controls. Members of the Dutch liver patient association completed the Liver Disease Symptom Index, Short Form-36, and Multidimensional Fatigue Index-20. We compared the HRQoL between patients with viral hepatitis, autoimmune hepatitis, cholestatic diseases, hemochromatosis and other liver diseases by linear, ordinal and logistic regression, corrected for disease stage and other significant factors. Viral hepatitis patients showed a worse mental health than other aetiological groups. Hemochromatosis patients demonstrated 17% more bodily pain than viral hepatitis patients and the strongest decrease in role emotional health with increasing age. Aetiological groups showed a worse generic HRQoL and more fatigue than controls. In conclusion, viral hepatitis and hemochromatosis patients have a more impaired HRQoL than patients of other liver disease aetiological groups.     

茵陈蒿汤加减联合甘草酸二铵、熊去氧胆酸对淤胆型肝炎的疗效观察

摘 要 目的：观察茵陈蒿汤加减联合甘草酸二铵、熊去氧胆酸治疗淤胆型肝炎的临床疗效和安全性,为淤胆型肝炎的临床治疗提供用药参考。 方法: 150例淤胆型肝炎住院患者随机分为对照组75例与观察组75例。对照组患者给予甘草酸二铵和熊去氧胆酸治疗,观察组患者在对照组治疗的基础上给予茵陈蒿汤加减,水煎,早晚分2次温服。两组疗程均为8周。观察两组患者的临床疗效,比较两组治疗前后血清总胆红素（TBIL）、直接胆红素（DBIL）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、以及碱性磷酸酶（AKP）、谷氨酰基转移酶（GGT）等指标变化和药品不良反应发生情况。结果: 观察组患者总有效率显著高于对照组（P<0.05）。治疗后两组患者TBIL、DBIL、ALT、AST、AKP、GGT等指标水平均较本组治疗前显著下降,且观察组显著低于对照组,差异有统计学意义（P<0.05）。两组患者治疗期间均未见明显不良反应发生。结论: 茵陈蒿汤加减联合甘草酸二铵、熊去氧胆酸治疗淤胆型肝炎疗效显著,安全性较好,可以作为临床治疗淤胆型肝炎的有效方法。