Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Intense pulsed light vs. pulsed‐dye laser in the treatment of facial acne: a randomized split‐face trial

Background Various laser and light therapy have been increasingly used for the treatment of acne vulgaris. Patients and methods Twenty patients with facial acne were treated using intense pulsed light (IPL) on one side of the face and pulsed dye laser (PDL) on the other to compare the efficacy and safety of IPL and PDL. Treatment was performed 4 times at 2‐week intervals. Treatment effectiveness was determined using lesion counts, acne severity, patient subjective self‐assessments of improvement, and histopathological examinations, which included immunohistochemical staining for transforming growth factor‐β (TGF‐β). Results Numbers of total acne lesions decreased following both treatments. For inflammatory lesions such as papules, pustules and nodules, IPL‐treated sides showed an earlier and more profound improvement than PDL‐treated sides. However, at 8 weeks after the 4th treatment, a rebound aggravation of acne was observed on IPL‐treated sides. On the contrary, PDL produced gradual improvements during the treatment sessions and these improvements lasted 8 weeks after the 4th treatment. Non‐inflammatory lesions as open and closed comedones also showed improvement following both treatments and PDL‐treated sides showed better improvement as the study proceeded. Histopathological examinations showed amelioration in inflammatory reactions and an increase in TGF‐β expression after both treatments, which were more prominent for PDL‐treated sides. Conclusion Both PDL and IPL were found to treat acne effectively, but PDL showed a more sustained effect. TGF‐β might play a key role in the resolution of inflammatory acne lesions.     

SUBACUTE HEPATIC FAILURE-A CLINICAL PROFILE

A combined experience of 37 cases of subacute hepatic failure encountered in five major gastroenterology centres over a period of ten years is discussed. Majority (65%) were males with average age of 38 years. Maximum (54%) were in 5th decade. Jaundice (100%), abdominal distention (38.7%), swelling feet (64%), fever (54%), abdominal pain (54%), exhaustion (78.3%) were the major presenting features. Jaundice and ascites were present in all cases. Pedal oedema (78.3%), hepatomegaly (54%), splenomegaly (32.4%) and encephalopathy (27%) were the other important clinical features. Hypoalbuminemia and prolonged prothrombin time were significant laboratory findings in addition to hyperbilirubinemia and elevated ALT and AST. Hbs Ag was detected in 46%. Major complications encountered were renal failure (48.7%), spontaneous bacterial peritonitis (43.2%), other infections (43.2%), encephalopathy (43.2%) and upper gastrointestinal bleed (22%). 54% died during stay in hospital. To conclude subacute hepatic failure is potentially fatal condition.KEY WORDS: Subacute hepatic failure, HBsAg, Jaundice     

Fas分子与肝细胞凋亡

近年来细胞分子生物学领域中的两个重要进展,即细胞凋亡概念的提出和Ｆａｓ分子的分离与鉴定对肝病的研究有重要影响,加深了人们对肝细胞损伤与死亡的认识．１９９３年Ｏｇａｓａｗａｒａｅｔａｌ［１］进行的Ｆａｓ单抗毒性实验证实了Ｆａｓ分子系统在肝细胞凋亡或损伤...     

替加环素和其他广谱抗菌药物对产丝氨酸碳青霉烯酶和金属β内酰胺酶的肠杆菌科细菌的抗菌活性:SENTRY监测网络的报告

肠杆菌科细菌对碳青霉烯类抗生素的耐药性可以由过量产生AmpC酶且同时外膜孔道蛋白大量缺失和（或）外排泵过量表达,或产生能水解碳青霉烯类的β内酰胺酶引起。这些碳青霉烯酶可以分为金属β内酰胺酶（MSL）和丝氨酸碳青霉烯酶两类。替加环素是一类半合成的甘氨酰环素类抗菌药物,对其他类抗生素耐药的细菌通常对替加环素无交叉耐药。     

刺蒺藜果中一种新桂皮酰胺类成分的分离和鉴定

从刺蒺藜(Tribulus terrestris L)果实中分得两个化合物,经理化常数测定和光谱(UV,IR,¹HNMR,¹³CNMR,¹H-¹³CCOSY和MS)解析。化合物I鉴定为N-对羟基苯乙酮基-3-甲氧基-4-羟基取代桂皮酰胺,为一新化合物,命名为蒺藜酰胺(terrestriamide)。化合物II为8-甲基氢化茚酮-1,首次从该植物中获得。     

7-(1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-甲酰氨基)头孢菌素的合成

本文报道了以1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-羧酸,用混合酸酐法与7-ACA,7-ADCA,7-ACT和7-ACD缩合,合成了24个1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-甲酰胺头孢菌素衍生物,通过葡聚糖凝胶(Sephadex LH-20)及离心薄层层析纯化精制,得到纯品。体外抑菌试验结果表明:大多数新头孢菌素衍生物对革兰氏阳性菌具有较好的抗菌作用。尚有一些新头孢菌素衍生物对某些革兰氏阴性菌具有中等敏感程度。     

7β-(6-取代-2-喹诺酮-3-乙酰氨基)头孢菌素的合成

以6-取代-2-喹诺酮-3-乙酸为侧链,用CDI法和潘化酯法与7-ADCA,7-ACA,7-ACT,和7-ACD缩合,合成了16个新的7β-(6-取代-2-喹诺酮-3-乙酰氨基)头孢菌素类化合物,通过溶媒转提,葡聚糖凝胶(Sephadex LH-20)柱层析及离心薄层层析分离精制,得到纯品。初步体外抑菌试验表明:新化合物对革兰氏阳性及某些阴性菌具有高度敏感性。大多数化合物对所试试验菌的抗菌活性与头孢唑啉和青霉素G钠相当,有些比它们还强。     

商陆多糖Ⅰ联合白细胞介素2对小鼠脾细胞杀瘤活性的影响

商陆多糖Ⅰ(PAP-I),0.3～3μg·ml^-1和小鼠脾细胞培养3～5d可显著增强其杀伤P815肿瘤细胞活性及IL-2(250～500IU·ml^-1)诱导的LAK细胞活性,最适浓度为1μg·ml^-1。PAP-I及IL-2和脾细胞培养的上清液对P815肿瘤细胞无细胞毒作用,但能增强脾细胞及LAK细胞杀瘤活性。PAP-I,5,10及50mg·kg-1,ip可增强脾细胞杀伤P₈₁₅和L₉₂₉细胞的活性及IL-2诱导的LAK细胞活性。