阿苯达唑脂质体治疗包虫病的初期临床观察

目的：评价阿苯达唑脂质体（L－ABZ）口服液的临床疗效及药物副作用，为该药的临床应用提供依据。方法：选择53例包虫病患者，分为3组：A组为单纯服药组（35例），连续口服L－ABZ 3－6个月；B组为包虫囊肿穿刺前后服药组（4例），穿刺前3－7d开始服药，穿刺后连服1个月；C组为手术前后服药组（14例），术前3－7d开始服药，术后可进食水后即开始服药，疗程1个月。3个治疗组服药剂量均为每天10mg/kg，2次／d。同时动态随访病人服药前后的血常规、肝肾功、胸部X线片、B超或CT以及病人对药物的毒副反应。用治愈率、有效率、部分有效率和无效率来衡量A组的疗效。以复发率（观察至少1年）来判断B、C组的疗效。结果：A组治愈16例（45．7％），有效9例（25．7％），部分有效6例（17．1％），无效4例（11．4％），总有效率88．6％；B组、C组随访时间1－3年，尚无复发。临床药物治疗的53例服药病人中，尚未见因药物的副反应而终止治疗的病例。结论：阿苯达唑脂质体（L－ABZ）口服液对包虫病病人疗效较为肯定，毒副反应轻，患者能够长期服用，尤其适用于某些不宜施行手术治疗或复杂的包虫病例。     

肝移植患者术后早期精神症状的观察

目的探讨肝脏移植术后早期精神系统并发症发生的原因和防治经验。方法回顾性分析 12 5例原位肝脏移植患者的临床资料 ,以术后 2周作为观察时点 ,分析肝脏移植术后早期精神系统并发症发生的原因 ,总结防治经验。结果有症状组和无症状组在性别、年龄、肝功能以及血环孢素A浓度方面无明显差异 ;但有症状组的无肝期时间 (93 74± 2 8 98)min和手术时间 (4 14 6 5±6 1 92 )min却长于无症状组 (P <0 0 5 ) ;另外 ,术前有无肝性脑病、术后感染以及静脉使用免疫抑制剂和术后精神症状的发生明显相关。结论肝脏移植术后早期精神系统并发症发生的原因是多方面的 ,通过积极的对症支持治疗 ,预后良好。     

Oral and maxillofacial surgery in patients with chronic orofacial pain.

PURPOSE: In this investigation, we evaluated a population of patients with chronic orofacial pain who sought treatment at a pain center in an academic institution. These patients were evaluated with respect to 1) the frequency and types of previous oral and maxillofacial surgery procedures, 2) the frequency of previous significant misdiagnoses, and 3) the number of patients who subsequently required surgical treatment as recommended by an interdisciplinary orofacial pain team. The major goal of this investigation was to determine the role of oral and maxillofacial surgery in patients with chronic orofacial pain. Patients and Methods: The study population included patients seen at the Center for Oral, Facial and Head Pain at New York Presbyterian Hospital from January 1999 through April 2001. (120 patients; female-to-male ratio, 3:1; mean age, 49 years; average pain duration, 81 months; average number of previous specialists, 6). The patient population was evaluated by an interdisciplinary orofacial pain team and the following characteristics of this population were profiled: 1) the frequency and types of previous surgical procedures, 2) diagnoses, 3) the frequency of previous misdiagnoses, and 4) treatment recommendations made by the center team. RESULTS: There was a history of previous oral and maxillofacial surgical procedures in 38 of 120 patients (32%). Procedures performed before our evaluation included endodontics (30%), extractions (27%), apicoectomies (12%), temporomandibular joint (TMJ) surgery (6%), neurolysis (5%), orthognathic surgery (3%), and debridement of bone cavities (2%). Surgical intervention clearly exacerbated pain in 21 of 38 patients (55%) who had undergone surgery. Diagnoses included myofascial pain (50%), atypical facial neuralgia (40%), depression (30%), TMJ synovitis (14%), TMJ osteoarthritis (12%), trigeminal neuralgia (10%), and TMJ fibrosis (2%). Treatment recommendations included medications (91%), physical therapy (36%), psychiatric management (30%), trigger injections (15%), oral appliances (13%), biofeedback (13%), acupuncture (8%), surgery (4%), and Botox injections (1%) (Allergan Inc, Irvine, CA). Gross misdiagnosis leading to serious sequelae, with delay of necessary treatment, occurred in 6 of 120 patients (5%). CONCLUSIONS: Misdiagnosis and multiple failed treatments were common in these patients with chronic orofacial pain. These patients often have multiple diagnoses, requiring management by multiple disciplines. Surgery, when indicated, must be based on a specific diagnosis that is amenable to surgical therapy. However, surgical treatment was rarely indicated as a treatment for pain relief in these patients with chronic orofacial pain, and it exacerbated and perpetuated pain symptoms in some of them.     

Kinetic characteristics of ICI D1694: a quinazoline antifolate which inhibits thymidylate synthase.

The thymidylate synthase (TS) inhibitor ICI D1694 (N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N -methylamino]-2 - thenoyl)-S-glutamic acid) is a structural analogue of the substrate N5,N10-methylenetetrahydrofolate (5,10-CH2FH4) and is currently under clinical evaluation as a treatment for cancer. The compound is shown here to be a mixed non-competitive inhibitor of TS from murine leukemia (L1210) cells when 5,10-CH2FH4 is varied. This result suggests formation of an inactive complex between TS, 5,10-CH2FH4 and the inhibitor. Thus, binding to only one of the two active sites on the TS homodimer may be sufficient to prevent catalysis fully. Treatment of L1210 cells with ICI D1694 is known to cause intracellular accumulation of the tetraglutamate derivative which is shown here to have a 60-fold higher affinity for TS. The IC50 for inhibition of L1210 cell growth is below the Ki value of ICI D1694 for L1210 TS but above that of the tetraglutamate. The formation of polyglutamates and concentration of drug inside cells, therefore, seem to be responsible for biological activity.     

Compression plating for child and adolescent femur fractures.

Twenty-five children ranging in age from 6-16 years underwent AO compression plate fixation for treatment of a femur fracture. Generally, the most common reason for plate fixation was to simplify nursing care and rehabilitation of children with an associated severe head injury or polytrauma. Twenty-three fractures healed in 11 weeks on the average, most by periosteal bone formation. Leg length discrepancy was not a clinical problem. Nursing care and polytrauma rehabilitation were simplified in all children. We believe that plate fixation is a reasonable treatment option for femoral fracture care in children aged less than 11 years with severe head injury or associated polytrauma.     

Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.