Conversion of Ouabain-Induced Ventricular Tachycardia in Dogs with Epicardial Lidocaine: Pharmacodynamics and Functional Effects

Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 ± 4.2 (mean ± SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 ± 3.49-mg/kg dose) was only minimally diminished (–14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance.     

Epoxyalkanoyls as novel ACE inhibitors

The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC₅₀ values of 0.06≈5.5 μM.     

nm23基因在前列腺癌中的表达与癌转移的关系

应用ＬＳＡＢ免疫组织化学染色方法，研究转移抑制基因ｎｍ２３表达产物二磷酸核苷激酶（ＮＤＰＫ）在前列腺癌中的表达及其意义。结果表明，ＮＤＰＫ／ｎｍ２３在前列腺癌中有较高的表达，阳性率为５００％（２０／４０）。无前列腺癌转移者其阳性率为６６７％（１２／１８），有前列腺癌转移者其阳性率为３６４％（８／２２），两者比较差异有显著性（Ｐ＜００５），并与前列腺癌分化程度和临床分期有显著相关。因此，ｎｍ２３基因可能在前列腺癌形成及转移过程中起不同的调节作用，其表达程度与前列腺癌转移呈负相关，有可能成为评价前列腺癌病人预后的一项新指标。     

Successful Treatment of Adult T-cell Leukemia/Lymphoma with MACOP-B,M-FEPA and VEPP-B Combination Chemotherapy

A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 × 10⁴ cells/mm³. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.     

胃癌病人天然杀伤细胞活性监测

报道微量细胞毒试验——LDH 释放法用于对胃癌病人临床免疫的监测.测定100例正常人和50例胃癌病人外周血 NK 细胞毒.结果:正常人值为36.10±5.68,胃癌组中,10例早期胃癌为28.76±4.70,25例进展期胃癌为14.51±5.80,15例晚期胃癌为11.86±4.43,与正常人值比较,P 值分别>0.05,<0.01和<0.01.NK 细胞毒活性随胃癌病变的进展和肿瘤体积的增大而逐渐降低,手术切除肿瘤后可有不同程度回升,甚至恢复到正常水平。长期化疗能损伤 NK 活性.     

Knee arthroplasty using a cementless PCA prosthesis with a porous-coated central tibial stem. Clinical and radiographic review at five years

In 44 consecutive patients, 60 porous-coated anatomic total knee (PCA) prostheses with a porous-coated central tibial stem were implanted without using cement. The clinical results and bony remodelling have been assessed after five years' follow-up. The average Hospital for Special Surgery knee score was 33.1 before operation and 95.7 at the latest follow-up, while the average range of movement improved from 63 degrees to 123 degrees. No subsidence or migration of the components was seen. A radiodense line appeared around the components at six months to one year after the operation and became more dense with time. There was no evidence of bone resorption related to stress-shielding in the tibial plateau.     

CT造影剂碘海醇注射液的制备及动物实验

本文报道了非离子型Ｘ－ＣＴ造影剂碘海醇注射液的制备及动物实验结果。磺海醇的最大吸收波长λ＿（ｍａｘ）为２４４ｎｍ。讨论了温度、浓度对磺海醇溶液粘度的影响：粘度随温度的升高而下降，呈负线型相关；粘度随浓度（Ｃ）升高而激剧升高，与浓度的四次方呈线性相关：Ｖ＿（３７℃）＝４７２．５８９［Ｃ］￣４＋１．１２１（ｒ＝０．９９７７）Ｖ＿（３０℃）＝６６３．８１３［Ｃ］￣４＋１．１５２（ｒ＝０．９９９６）Ｖ＿（２０℃）＝１０８２．９５３［Ｃ］￣４＋１．４３３（ｒ＝０．９９８２）使用该注射液进行狗的造影实验，获得了清晰的造影图像。     

Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin

Study Objective . To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. Design . Randomized, double-blind, two-period, crossover study. Setting . University hospital clinical research unit. Patients . Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment. Interventions . Volunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later. Measurements and Main Results . Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording. Conclusions . Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.     

An efficient procedure for the regioselective synthesis of 10-methoxy-11-hydroxyaporphine from (R,S)-10,11-dihydroxyaporphine

A regioselective preparation of 10-methoxy-11-hydroxyaporphine (“Apocodeine,1b”) from (R,S)-10, 11-dihydroxyaporphine(apomorphine,1a) is described. The isopropylidene ketal ring of 10,11-(isopropylidenyldioxy) aporphine (2) obtained by the isopropylidenation of apomorphine, was regioselectively opened by the ten equivalent of trimethylaluminum to give 10-hydroxy-11-t-butyloxyaporphine (3). The free 10-hydroxyl position of 3 was methylated with methyl p-toluenesulfonate/NaH, and afforded 10-methoxy-11-t-butyloxyaporphine (4) in high yield. Selective debutylation gave the desired 10-methoxy-11-hydroxyaporphine (“apocodeine”,1b) in good yield.     

Retinopathy of prematurity in infants less than 29 weeks' gestation at birth

From January 1986 to December 1991 we examined the eyes of 206 infants born at Westmead Hospital, Neonatal Intensive Care Unit who were less than 29 weeks' gestation at birth to determine the incidence of retinopathy of prematurity. Eighty-five infants (41.3%) had no retinopathy of prematurity (ROP) in either eye, 82 infants had stages 1 or 2 ROP (39.8%), 29 had stage 3 ROP (14.1%) and 11 had stage 4 ROP (5.3%). Of these, cryotherapy was performed in 18; six now have bilateral retinal detachment and are blind The more severe stages of ROP were significantly associated with an increase in the number of days of oxygen supplementation, an increase in the number of days of mechanical ventilation and the presence of patent ductus arteriosus. Infants receiving steroids for mechanical ventilator dependence had a significantly greater chance of requiring cryotherapy (11 or 22 receiving steroids versus seven of 43 without steroids; P < 0.01).