Hepatic falciform artery

The hepatic falciform artery is an occasional terminal branch of the left or middle hepatic artery, and may provide an uncommon but important collateral route when the principal visceral arteries are occluded.     

抗结核药物所致皮疹临床特点及停药指征的探讨

目的 探讨抗结核药物所致皮疹的临床特点及停药指征.方法 对1998-2005年收治的3 082例住院结核病人中,因抗结核药物所致皮疹296例病人进行分析.结果 变态反应总发生率为10.3%,皮疹发生率为9.6%（296例）,其中单纯皮疹88例,占2.9%,皮疹伴其他系统表现一种或一种以上者208例,占6.7%;无皮疹者22例,占0.7%.皮疹病例总停药率为61.5%.结论 抗结核药物所致过敏反应多为全身性,发生过敏反应后,绝大多数单纯皮疹病人经过抗过敏处理后仍可维持原方案继续治疗,而皮疹伴有明显肝功能异常、心律失常、关节痛和过敏性休克者均需立即停用抗结核药物,并且避免再次使用.     

Dermatitis in bulb growers

A damaged skin forms a health hazard in flower-bulb growers as it enables higher permeation rates For pesticides than normal skin. Therefore, an investigation was performed into the skin condition of 103 bulb growers and 49 controls. Contact dermatitis of the hands was of the same order (11 and 10%) in both groups. However, minor signs of dermatitis were seen more often in bulb growers (30 versus 8%, p <0.05). Most growers had contact with narcissus sap during the investigation. This irritant sap, as well as many other skin contacts with irritants such as hyacinth dust and pesticides, seemed to be responsible for many skin complaints. Contact serialization was suspected in 19 growers and 3 controls. Patch tests showed that contact sensitization existed to pesticides in probably 10, and to flower-bulb extracts in 4 growers. Reactions to propachlor were not regarded as very reliable as the test concentration seemed to be marginally irritant. There were only a few allergic reactions to narcissus (3) and tulip (2) and none to hyacinth. This investigation showed that minor irritant contact dermatitis was frequent in bulb growers, and indicated that contact sensitization to pesticides and bulbs seemed to be a less frequent but important cause of dermatitis.     

Cardiovascular and respiratory mechanisms in anaphylactic and anaphylactoid shock reactions

Summary Different mediators such as histamine, leukotrienes, prostaglandins and bradykinin are involved in different reaction mechanisms such as cytotropic anaphylaxis (CA), immune complex anaphylaxis (ICA), reactions due to direct histamine liberation or activation of the complement system or hyperosmolarity induced anaphylactoid reactions.In the monkey CA induces systemic vasodilatation, a transient pulmonary hypertension and increase of cardiac output followed by peripheral blood pooling and depression of cardiac output. ICA induces peripheral vasoconstriction, a severe increase in pulmonary vascular resistance and decreased cardiac output, the latter possibly being partially due to decreased cardiac contractility.In hypersensitivity reactions in man cutaneous vasodilatation as well as vasoconstriction may occur alternatively. Peripheral blood pooling and increased vascular permeability are the cause of severe relative and absolute hypovolemia, respectively. Pulmonary vasoconstriction seems to occur in connection with serious bronchospasm. Decreased venous return, myocardial ischemia and hypoxemia can contribute to a reduction of cardiac performance. The most frequent changes in the ECG are sinus tachycardia, sinus bradycardia, extrasystoles, conduction disturbances as A-V block and bundle branch block; lethal or sublethal shock is often associated with malign arrhythmias or cardiac arrest.Almost normal blood gas values are seen in anaphylactic shock without clinical signs of respiratory obstruction. The very few documented cases of anaphylactic shock with respiratory obstruction indicate that increased airway resistance and reduced lung compliance may be present as well as mild to moderate hypoxemia with normal or subnormal CO₂ values.     

539例麻疹疑似病例血清学监测分析

目的了解麻疹的血清流行病学特征,探讨麻疹与风疹之间的血清学鉴别诊断。方法采用酶联免疫吸附法对539例麻疹疑似病例的血清标本进行麻疹IgM和风疹IgM抗体检测。结果539例麻疹疑似病例中7岁前发病占61.0%,而20岁以后发病仍占25.0%。麻疹IgM阳性率为82.6%(445/539),风疹IgM抗体阳性率为1.1%(6/539),以麻疹为主。各年龄组麻疹IgM抗体检测阳性率经2χ检验(2χ=2.895,P=0.576),无统计学意义。在出疹后第2天前(0～1d)采集的血清标本其麻疹IgM抗体阳性检出率为72.9%,从出疹后第3天至14天(2～14d)采集的血清标本其麻疹IgM抗体检测阳性率为88.4%,两者之间经2χ检验有统计学意义(2χ=21.08,P<0.001)。结论本地发热出疹性疾病以麻疹为主;发病年龄分布主要在7岁前,而20岁以后仍然占相当大比例,值得注意;采血时间与检出率密切相关;仍然有16.3%的疑似病例未经过实验室确诊,应提高麻疹实验室诊断的及时性、准确性和敏感性,建议采集双份血(即采集急性发病期及恢复期血清),对麻疹IgM和风疹IgM抗体检测阴性结果的病例,再进行双份血IgG测定,以提高麻疹疑似病例确诊性。     

Risk of mucocutaneous toxicities in patients with solid tumors treated with sunitinib: a critical review and meta analysis

Introduction: we performed a systematic review and meta-analysis of mucocutaneous toxicities associatedwith sunitinib, an oral multi-tyrosine kinase inhibitor. Methods: eligible studies included randomized Phase II and III trials of patients with solid tumors on sunitinib daily, describing events of hand–foot syndrome, skin rash, stomatitis, and skin and hair discoloration. Results: the relative risk (RR) of all-grade hand–foot skin reaction, skin rash, stomatitis, skin and hair discoloration were 2.12 (95% CI: 1.28–3.51; p < 0.004), 1.33 (95% CI: 1.15–1.54; p < 0.0002), 1.88 (95% CI: 1.36–2.59; p = 0.0001), 16.6 (95% CI: 4.18–64.94 p < 0.003), 4.42 (95% CI: 0.8–24.5; p < 0.09); respectively. Conclusions: our meta-analysis has demonstrated that sunitinib is associated with a higher risk of developing all-grade hand–foot skin reaction, skin rash, stomatitis and skin discoloration compared with control. Clinicians should be aware of these risks and perform regular clinical monitoring.     

Skin rash induced by ritonavir-boosted darunavir is common,but generally tolerable in an observational setting

Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor widely used in the treatment of HIV-1 infection. However, skin rash is a well-known adverse event of DRV, and limited data are available from observational settings. This observational study examined the characteristics of DRV-induced skin rash in treatment-naïve patients who commenced once-daily DRV/r-containing antiretroviral therapy (ART). Of the 292 study patients, DRV rashes developed in 31 (11%) patients with a median latency of 10 days (developing from 7 to 14 days in 93%) from initiation of ART. DRV skin rash was generally mild, as only one patient (3%) had grade 3 rash whereas 24 (77%) patients had grade 2 and 6 (19%) patients had grade 1. Only two patients (7%) discontinued DRV/r due to skin rash, and the other continued DRV/r and their rashes disappeared completely without any complications. Interestingly, DRV rash occurred more frequently to patients with less advanced HIV-1 infection than those with advanced infection. The incidence of DRV rash was not significantly different between patients with and without history of sulfonamide allergy (p = 0.201). Furthermore, when we exclude patients without history of sulfonamide use and only examine patients with sulfonamide use (n = 145), the result was similar (p = 0.548). In conclusion, DRV rashes were frequently observed but the prognosis was benign. Most patients tolerated DRV rashes with use of oral steroid or antihistamine without discontinuation of DRV. To date, there is no clear clinical evidence to suggest that DRV should be avoided in patients with history of sulfonamide allergy.     

Case-Control Exploration of Relationships Between Early Rash or Liver Toxicity and Plasma Concentrations of Nevirapine and Primary Metabolites

Abstract

Objective: This investigation measured trough nevirapine and five oxidative metabolite concentrations in plasma specimens collected from patients who exhibited a rash or liver function abnormality during the first 6 weeks of treatment. Method: Patient selection came from three clinical trials, totaling 1,357 patients, from which frozen specimens had been stored and were available for assay. The control patients were matched according to trial, steroid use, CD4 cell count, gender, race, and hepatitis B/C status. Observed plasma metabolite concentrations were compared using signed rank tests. Results: A total of 49 case-control pairs were studied. Women had significantly greater exposure than men to nevirapine and four of the five metabolites at week 2, but the plasma concentrations were comparable by week 4. Steroid (prednisone) co-medication produced significantly different plasma nevirapine and metabolite concentrations for the majority of case-control comparisons at week 3, a week after cessation of steroid treatment, but only occasionally produced a measurable difference at other weeks. Conclusion: During the first 6 weeks of nevirapine therapy, the rashes and liver enzyme elevations that occurred appear to be idiosyncratic. There were no strong relationships observed between the plasma concentrations of nevirapine or any of its five metabolites to a casedefining event. The systemic exposure of the metabolite 12-hydroxynevirapine and its successor 4-carboxynevirapine, hypothesized in the skin rash female Brown Norway rat model as reactive intermediates for idiosyncratic immune-mediated adverse reactions, were comparable between case and control samples and were comparable in proportion to the precursor nevirapine exposure.     

Nevirapine-induced liver lipid-SER inclusions and other ultrastructural aberrations

Nevirapine (NVP) therapy is associated with a high risk of serious liver injury and skin rash. Treatment of Brown Norway rats with NVP causes an immune-mediated skin rash. Even though NVP does not cause serious liver injury in wildtype animals, incubation of hepatocytes with NVP leads to the release of presumably danger-associated molecular pattern molecules (DAMPs), which activate macrophages. In this study, we examined the liver biopsies of Brown Norway rats treated with NVP to determine the histologic correlate to the release of DAMPs by hepatocytes. In vivo, debris from necrotic hepatocytes and endothelial cells were present in the liver sinusoids, a condition that can trigger an immune response. In addition to mitochondrial, hepatocytic, and endothelial damage, the drug induced large hepatocytic inclusions composed of lipid droplets surrounded by concentric whorls of smooth endoplasmic reticulum (SER) cisternae—lipid-SER (LSER) inclusions, which were deposited in the sinusoids. NVP is lipid soluble, and these LSER inclusions may be sinks of NVP or its metabolites. LSERs are deposited in the blood stream where they may be picked up by lymph nodes and contribute to initiation of an immune response leading to serious liver injury or skin rash. LSERs migration from liver to the blood stream may signify a novel mechanism of drug exocytosis.