Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses.

A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.     

黑柴胡中新三萜皂甙的结构鉴定

从黑柴胡(Bupleurum smithii Wolff)根中分离出10个化合物,均为首次由该植物中获得。其中二个新三萜皂甙,即柴胡皂甙k和l(saikosaponin k and l),其结构经紫外、红外、核磁共振氢谱,碳谱和质谱等波谱测定和解析,分别确定为3β,16β,23,28-四羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃木糖基-(1→2)-β-D-吡喃葡萄糖基-(1→3)-β-D-吡喃呋糖甙和3β,16α,23,28,30-五羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基-(1→3)-β-D-吡喃呋糖甙。     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections

BACKGROUND: Anesthesia for the child who presents for surgery with an upper respiratory infection (URI) presents a challenge for the anesthesiologist. The Current prospective study was designed to determine the incidence of and risk factors for adverse respiratory events in children with URTs undergoing elective surgical procedures. METHODS: The study population included 1,078 children aged 1 month to 18 yr who presented for an elective surgical procedure. Parents were given a short questionnaire detailing their child's demographics, medical history, and presence of any symptoms of a URT. Data regarding the incidence and severity of perioperative respiratory events were collected prospectively. Adverse respiratory events (any episode of laryngospasm, bronchospasm, breath holding > 15 s, oxygen saturation < 90%, or severe cough) were recorded. In addition, parents were contacted 1 and 7 days after surgery to determine the child's postoperative course. RESULTS: There were no differences between children with active URIs, recent URIs (within 4 weeks), and asymptomatic children with respect to the incidences of laryngospasm and bronchospasm. However, children with active and recent URIs had significantly more episodes of breath holding, major desaturation (oxygen saturation < 90%) events, and a greater incidence of overall adverse respiratory events than children with no URIs. Independent risk factors for adverse respiratory events in children with active URIs included use of an endotracheal tube (< 5 yr of age), history of prematurity, history of reactive airway disease, paternal smoking, surgery involving the airway, the presence of copious secretions, and nasal congestion. Although children with URIs had a greater incidence of adverse respiratory events, none were associated with any long-term adverse sequelae. CONCLUSIONS: The current study identified several risk factors for perioperative adverse respiratory events in children with lulls. Although children with acute and recent URIs are at greater risk for respiratory complications, these results suggest that most of these children can undergo elective procedures without significant increase in adverse anesthetic outcomes.     

Nicotine and cotinine in adults' urine: The German Environmental Survey 1998

In 1998, the German Environmental Survey (GerES III) recruited approximately 5000 adults between the ages of 18 and 69 years. The study population for these analyses consisted of 1580 smokers (34% of the total population) and 3126 nonsmokers. Nicotine and cotinine concentrations in urine were determined by HPLC methods with UV-detection and corrected for creatinine. Nicotine and cotinine concentrations differed between smokers and nonsmokers by factors of 10-100. The multiple linear regression models used for the analyses of nicotine detection in the urine of smokers explained 43.2% and 42.3% of the total volume-specific and creatinine-specific variances, respectively. Cigarette smoking was the major factor responsible for 41% of the total variance. The explained variances of the cotinine results were larger, 51.0% and 49.3% of the total variance were volume-specific and creatinine-specific, respectively. More than 20% of nonsmokers in GerES III were exposed to environmental tobacco smoke at home, at work or in other places. The logistic regression analysis approach used for the group of nonsmokers showed the greatest effects for those exposed to tobacco smoke at home (adjusted OR varied between 4 and 6). These results were seen for nicotine as well as for cotinine excretion. Exposure to tobacco smoke in the workplace doubled the risk for the detection of nicotine and cotinine in urine. When other risk factors such as age, sex, social status, community size, season of urine collection, and the consumption of food containing nicotine such as potatoes, cabbage, tea were included, the effect estimates for tobacco smoke exposure remained unchanged. A new federal bill to diminish environmental tobacco smoke (ETS) exposure in the workplace was recently passed in Germany, but protection of nonsmokers from smoking family members at home needs more attention.     

Chronic venous insufficiency due to great saphenous vein incompetence treated with radiofrequency ablation: an effective and safe procedure in the elderly

Chronic venous insufficiency (CVI) with the resultant clinical sequelae significantly reduces quality of life. Most elderly patients with CVI are treated nonoperatively owing to concerns of increased operative risk and therefore suffer more advanced disease. Radiofrequency ablation (RFA) has emerged as a minimally invasive procedure to treat patients with superficial venous insufficiency (SVI) due to great saphenous vein (GSV) incompetence. The purpose of this study was to review our experience using RFA of the GSV to treat CVI due to superficial disease in elderly patients compared to younger patients in terms of procedure-related morbidity and severity of disease at time of treatment. RFA treatment of the GSV was performed in 490 extremities of 421 patients with SVI between March 2001 and December 2002. Indications, medical history, and outcome (operative complications and hospital stay) were compared between 2 groups: Group I:41 extremities of 35 patients, 70 years if age or older (mean 75 +/-4); and Group II:449 limbs of 386 patients younger than 70 years (mean 47 +/-11). The incidence of skin pigmentation and healed/nonhealed ulcers (CEAP 4-6) was significantly higher in the elderly than in the younger group (41% vs 16%, p <0.05). Hypertension, diabetes, and previous myocardial infarction were 2.8, 5.4, and 6.7 times more prevalent in the elderly (p <0.05), respectively. There were no major postoperative complications in either group; 97% of all patients were discharged on the day of operation and there was no difference between the 2 groups in overnight hospital stay. There is a treatment bias against operative management in elderly patients with SVI, as evidenced by their more advanced disease at the time of definitive treatment than their younger cohort. However, operative morbidity is no different compared to the younger subset. RFA is a safe and effective procedure for older patients; therefore, the threshold for operative management of older patients should be lowered.