Identification of immunoreactive monoclonal antibody fragments for improved immunoscintigraphy

Results obtained in animal models suggest that antibody fragments may have advantages over whole immunoglobulin for in vivo localisation studies. Proteolytic digestion of monoclonal antibodies may however yield a mixture of products unsuitable for in vivo use. This report describes a method whereby the immunoreactive products of antibody digestion can be identified by probing nitrocellulose blots of the gel-separated digest with the specific antigen. Optimum conditions for the production of the reactive fragments can then be determined and once identified they can be purified to homogeneity. Using this method conditions have been defined for the production of F(ab)2 and Fab fragments from a papain digest of an antibody to placental alkaline phosphatase (H17E2). In this case the antigen has enzyme activity which can be used to detect binding to the immunoreactive bands on the Western blots. In vivo experiments in nude mice carrying xenografts of a tumour expressing the H17E2 reactive antigen were performed to determine the efficacy of localisation of the purified fragments as compared to the whole antibody. As expected the absolute levels of radioactivity localised in the tumour was highest using whole antibody, whereas the F(ab)2 fragments produced the highest tumour:blood ratios.     

Post-operative thoracic irradiation with or without levamisole in non-small cell lung cancer: results of a Radiation Therapy Oncology Group Study

The Radiation Therapy Oncology Group conducted a Phase III single blind trial to evaluate the addition of Levamisole to post-operative thoracic irradiation (200 cGy five times weekly to a total of 5000 cGy plus 1000 cGy boost) in patients with resected RTOG Stage II-III non-small cell lung cancer with positive nodes. Between February 1980 and February 1983, 74 patients from 18 RTOG institutions were randomized; accrual to this study was prematurely terminated due to poor accrual and the inferior survival observed in the levamisole-treated patients on another RTOG trial. Sixty-four patients were evaluable; 32 assigned to levamisole and 32 were assigned to placebo. Over 95% of the patients have been followed for a minimum of 4 years or to death. Two patients on placebo and 5 on levamisole experienced Grade 3 pneumonitis or esophagitis; 1 patient on placebo and 2 on levamisole experienced Grade 3 pulmonary fibrosis. Three patients on levamisole experienced other Grade 3 or 4 toxicity: 1 case of intractable nausea and vomiting and 2 with Grade 4 neutropenia (less than 500 per mm3). There were no fatal complications. Median disease-free survival was 13 months in the placebo group and 9 months for the levamisole group. Median time to distant metastases was 18 and 12 months, and median survival was 20 and 13 months, respectively. We concluded that this study failed to demonstrate an advantage for levamisole.     

Secretory surface area and phosphatase activity of frog gastric mucosa.

Gastric mucosae were isolated from the European frog, R. temporaria, and after 5-7 h, stimulated with histamine (10(-4) M) and theophylline (5 mM). Acid secretion increased about fourfold, and this was accompanied by a threefold increase in secretory surface of the oxyntic cells, as determined in electron micrographs with conventional morphometric techniques. At the same time phosphatase activity of the secretory surface increased. Other experiments showed that the latter was due to an acid phosphatase, with pH optimum near 3. It appears that the increase in surface phosphatase with stimulation can be attributed to a diminished local pH and not to the increase in surface area demonstrated in this study.     

术中胆道造影在腹腔镜胆囊切除术中发现胆道损伤的作用

目的：评估术中胆道造影（IOC）在早期发现腹腔镜胆囊切除术（LC）术中胆道损伤的作用。方法：回顾分析31例LC术后胆道损伤的部位，机理，诊断时间，治疗方法及结果，并对是否行IOC进行评估。结果：胆道错认引起胆道损伤共19例，其中12例IOC显示胆道错认，致胆道部分切开损伤，腹腔镜下行I期修复或开腹修复，T管引流，但无并发症。19例中3例IOC误读及4例未行IOC患者中发生迷走胆管损伤2例，胆总管完全离断1例，胆总管完全离断合并胆道缺损2例，本组有2例损伤发生于IOC后，结论：行IOC并正确阅读可及时发现腹腔镜胆囊切除术中胆道错认所致的胆道损伤，从而防止随之可能发生的严重并发症。     

Verapamil as an adjunct to local anaesthetic for brachial plexus blocks

Background: Calcium channel blockers potentiate the effects of local anaesthetics. We examined the effect of adding verapamil to local anaesthetic solution on anaesthetic duration in patients undergoing surgery under brachial plexus block.     

Short‐ and long‐term vertical diplopia secondary to blunt trauma

This report describes the short‐ and long‐term ocular signs and symptoms of a patient with an orbital blow‐out fracture and discusses the differential diagnosis of vertical diplopia. A blow‐out fracture occurs when blunt trauma is applied either directly to the eyeball itself or the orbital rim and usually results in a fracture of the orbital floor with consequential excavation and entrapment of orbital contents in the fracture. Vertical diplopia is a common presenting symptom for a blow‐out fracture of the orbit but careful considerations should be given to other potential conditions leading to such diplopia. A patient is presented who suffered a blow‐out fracture almost a decade earlier, secondary to blunt trauma to the globe. The clinical findings are provided immediately after the trauma, post‐surgery and during a recent ocular examination.     

绝经后女性类风湿关节炎患者骨密度变化影响因素分析

目的探讨绝经后女性类风湿关节炎(RA)患者发生骨质疏松(OP)的原因。方法收集63例绝经后女性RA患者一般临床资料、疾病活动相关指标、手足X线资料,并同时测量患者7个部位的骨密度。结果23例患者(36.5%)有至少一处检测部位表现为低骨量。前臂和桡尺骨远端的低骨密度发生率(23.8%)与OP总发生率(28.6%)无显著性差异(P>0.05)。OP的发生与疾病活动指标及糖皮质激素的使用均无相关性。多元回归分析显示绝经的年限和关节腔狭窄为低骨量发生的独立危险因素(P<0.05);而雌激素替代疗法(HRT)为低骨量发生的唯一保护因素(P<0.05),小剂量糖皮质激素对本组患者的骨密度无影响。结论OP是绝经后女性RA患者的常见并发症,绝经年限长和关节破坏严重是低骨量发生的独立危险因素,HRT是防治低骨量的保护因素。     

Gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux in very low birthweight infants was studied using a new 1 mm monocrystalline antimony oesophageal pH electrode. Gastro-oesophageal reflux was detected in 30 (85%) subjects. The mean (SEM) number of episodes of reflux in 24 hours was 12.1 (2.1), and 3.2 (0.6) lasted over five minutes. The mean reflux index was 4.5 (1.0)%, and the longest episode 17.1 (4.6) 17.1. Reflux was unrelated to postconceptional age or to resting lower oesophageal sphincter pressure. The mean reflux index was low at rest before feeds, being 1.8 (0.6)%, and increased slightly after feeds (3.8 (1.0)%), but was significantly increased after nursing care to 16.4 (3.0)%, and while xanthines were being given (5.9 (1.6)%. A subgroup of seven infants with xanthine resistant apnoea had severe gastro-oesophageal reflux that was not clinically apparent (reflux index 27.4 (3.6)%). Successful treatment of the reflux (reflux index: 3.6 (1.2)%) was associated with cessation of the apnoea. We conclude that gastro-oesophageal reflux is common, and is usually not clinically apparent, even when severe. It is important to consider gastro-oesophageal reflux in the differential diagnosis of xanthine resistant apnoea in preterm infants.     

Determinants of condom use among junior high school students in a minority, inner-city school district.

Condoms reduce the risk of human immunodeficiency virus (HIV) transmission; however, their use among adolescents has been inconsistent. Little is known about factors which motivate consistent condom use, particularly among younger adolescents. In a study designed to identify such factors, 1899 inner-city junior high school students were surveyed. In June 1988, students completed an anonymous self-report questionnaire assessing HIV-related knowledge, attitudes, and behaviors. Among sexually active students (N = 403), logistic regression analysis evaluated the influence of demographic, psychosocial, and behavioral factors on frequency of condom use. Respondents who believe condoms are effective in preventing HIV transmission were 2.2 times more likely to report using condoms consistently during sexual intercourse; those with low perceived costs associated with condom use were 1.9 times more likely to be consistent users. Number of lifetime sexual partners was inversely related to frequency of condom use. Respondents with a history of three or more sex partners were half as likely to use condoms consistently. Factors not associated with consistent condom use include age, age at sexual debut, ethnicity, HIV knowledge, perceived efficacy to avoid HIV infection, and alcohol and drug use. School- and community-based HIV prevention programs will have to go beyond the didactic transfer of factual information and include more interactive teaching strategies to improve adolescents' attitudes toward condoms are self-efficacy to increase condom use and to counter negative peer influences and adolescents' perceptions of invulnerability. Physicians are an underutilized source of HIV prevention information. They have an important role in counseling adolescents about effective HIV-prevention methods and dispelling misperceptions which hinder consistent condom use.     

African green monkeys provide a useful nonhuman primate model for the study of human parainfluenza virus types-1, -2, and -3 infection

Human parainfluenza virus (HPIV) types-1, -2, and -3 are significant causes of both upper and lower respiratory tract disease in infants and children. Although there are two live attenuated vaccines for the prevention of HPIV-3 disease in phase 1 clinical trials, vaccines are not currently available for prevention of HPIV-1 or -2 disease. Our laboratory is developing candidate vaccines for the prevention of HPIV-1, -2, and -3 disease, and a suitable nonhuman primate model is needed for evaluation of these vaccine candidates prior to administration to humans. We evaluated the replication of HPIV-1 and -2 in six different species of nonhuman primates and found both viruses to replicate most efficiently in African green monkeys and chimpanzees. We then compared the replication of HPIV-3 in African green monkeys to that in rhesus macaques, which we have used previously, and found that HPIV-3 replicated to higher titer in African green monkeys. In summary, African green monkeys provide a very useful nonhuman primate for the evaluation of HPIV-1, -2, and -3 vaccine candidates, especially for the evaluation of various combinations of these PIV vaccines and for vaccine strategies that employ sequential immunization.