Cytotoxicity Tests against Cultured Human Lung Cancer Cells With Autologous Lymphocytes Activated in vitro by Mitomycin C-Treated Tumor Monolayers in the Presence of T-Cell Growth Factor

Human peripheral blood or lymph node lymphocytes, obtained frompatients with a variety of lung cancer, were incubated in vitrowith mitomycin C-treated tumor monolayers in the presence ofT-cell growth factor. The cytotoxicity of these lymphocytesfor autologous tumor cells (autologous killer activity) wasassessed by a 4-hr ⁵¹Cr-release assay. Cytotoxic activity wasobserved in 14 out of a total of 20 cases. Lymphocytes frompatients with squamous cell carcinoma, large cell carcinomaand carcinoid exhibited positive activity levels of 11.1 ±1.8, 16.3 and 23.9% respectively. Nine out of 13 patients withadenocarcinoma exhibited positive activity with a mean valueof 8.8 ± 6.8%. No lymphocyte activity against small cellcarcinoma was observed. Natural killer (NK) activity did not always correlate with autologouskiller (AK) activity. Treatment of lymphocytes with monoclonalanti-human lymphocyte antibody revealed differences in effectorcell populations concerning these two activities; AK activitywas abrogated only by treatment with anti-human Lyt 3 antibodyand complement, whereas NK activity was abrogated by anti-humanLyt 1, 2 and 3 and partially by anti-human la antibody. Theseresults indicate that AK activity is mediated exclusively byT cells, but that NK activity is mediated by several subpopulationsof lymphocytes such as T cells, null cells and others.     

Cerulein-induced Pancreatic Polypeptide Secretion

Intramuscular administration of cerulein caused an abrupt rise in plasma pancreatic polypeptide (PP) in normal subjects. Pretreatment by atropine tended to lower the basal plasma PP level and significantly blunted the cerulein-induced PP secretion. It appears, therefore, that PP secretion induced by cerulein is under vagal control. In addition, in normal subjects, a gallbladder series first revealed a well-filled gallbladder of normal size and shape, which then contracted most strongly after a cerulein injection at a time corresponding exactly with the peak plasma PP levels produced by the cerulein. Since exogenous PP is known to cause a relaxation of the gallbladder, it is possible that endogenous PP plays an important role in gallbladder motility.     

Risk of Long‐Term Dual Antiplatelet Therapy Following Drug‐Eluting Stent Implantation in Octogenarians

Objectives

To evaluate the risk of long‐term dual antiplatelet therapy (DAT) following drug‐eluting stent (DES) implantation in octogenarians.

Background

DES implantation requires DAT; however, DAT‐associated risk in octogenarians remains unclear.

Methods

Two‐hundred and six consecutive octogenarians (130 men, 83.3 ± 3.4 years) underwent stent implantation (104 bare metal stents [BMSs] and 102 DESs) and 38.0 ± 13.2 months of follow‐up.

Results

Significantly more DES patients received DAT. The incidence of bleeding events was similar in the DES and BMS groups for 1 year (total: 10.8% vs 5.8%, P = 0.19; major: 4.9% vs 2.9%, P = 0.70). However, after 2 years, significantly more bleeding events occurred in the DES group than the BMS group (total: 2 years, 21.6% vs 9.6%, P = 0.02; 3 years, 29.4% vs 11.5%, P = 0.001; 4 years, 31.4% vs 15.4%, P = 0.007; major: 2 years, 12.7% vs 3.8%, P = 0.04; 3 years, 18.6% vs 5.8%, P = 0.005; 4 years, 19.6% vs 6.7%, P = 0.006). Overall, significantly more total bleeding events (31.4% vs 15.4%, P = 0.007) and major bleeding events (19.2% vs 6.7%, P = 0.006) were observed in the DES group than in the BMS group. The adjusted hazard ratios and 95% confidence intervals (CI) were as follows: total bleeding events, 2.203 (95% CI: 1.065–4.556; P = 0.033); major bleeding events, 4.324 (1.506–12.414; P = 0.007).

Conclusions

DAT was associated with an increased risk of bleeding events in octogenarians after 2 years. DAT discontinuation should be considered for octogenarians 1‐year post‐DES implantation. (J Interven Cardiol 2013;26:114–122)

     

Insertion of a pacing lead via the tricuspid valve does not affect cardiac function and tricuspid valve regurgitation in young dogs

A preliminary experimental study in dogs was conducted to evaluate the feasibility of transvenous cardiac pacing in the fetus with complete heart block associated with hydrops. Four young mongrel dogs were anesthetized with intravenous administration of sodium pentobarbital and mechanically ventilated, and a pacing lead was inserted via the tricuspid valve. The right ventricular cardiac output, aortic pressure and central venous pressure were measured, and the tricuspid valve regurgitation was measured semi-quantitatively using echo-Doppler color flow imaging. The relationship between the location of the pacing lead and the tricuspid valve regurgitation and cardiac function was examined. The mean right ventricular cardiac output when the pacing lead was inserted into the superior vena cava (126 ± 54 mL/min per kg) was not significantly different from that when it was inserted into the right ventricle (110 ± 43 mL/min per kg). The aortic pressure was 66 ± 7.7 mmHg and 67 ± 6.6 mmHg, respectively, and the central venous pressure 5.9 ± 1.7 mmHg and 5.7 ± 1.6 mmHg, respectively, under the two conditions (not significantly different). The ratio of demonstrating significant tricuspid valve regurgitation was 4/13 into the superior vena cava and 5/13 into the right ventricle, respectively (not significantly different). The location of the pacing lead did not change the cardiac function or the amount of the tricuspid valve regurgitation in our experimental study. It was therefore concluded that the transvenous cardiac pacing technique has potential application in intrauterine transvenous cardiac pacing in the fetus with complete heart block.     

Biochemical characterization of tyrosinase inhibitors using tyrosinase binding affinity chromatography

Purification of tyrosinase inhibitors of hamster melanomas was carried out using tyrosinase binding affinity column chromatography. This method enables the isolation of tyrosinase inhibitors with a 124-fold purification index as compared to that of crude preparation after dialysation. The purified inhibitors consist of a mixture of 5000-6000 and a 310 molecular weight fraction. They also show characteristics of polypeptides which contain glycine, glutamic acid, serine, proline and alanine as main amino acids.     

Prognosis and clinical features of intractable epilepsy: A prospective study

Abstract  Of the epileptic patients who were treated for ≥ 5 years until the end of 1990 and had more than four seizures in 1990, 63 patients had been treated without interruption until the end of 1995. We analyzed their clinical courses from 1990 to 1995 prospectively. More than half the subjects were diagnosed with temporal lobe epilepsy. Twenty cases had presumed etiology, and 32 had neuropsychiatric complications. Of the subjects whose seizures were not controlled with conventional antiepileptic drugs (AED), 11 cases demonstrated significant improvement when new AED; that is, lamotrigine, vigabatrin, clobazam, topiramate, tiagabine or CGP33101 were added. However, 10 patients did not respond to new AED. Presumed etiology, neuropsychiatric complications, multiple epileptic foci in EEG and abnormalities on head CT or MRI were characteristics of the patients whose seizures were resistant to new AED.     

Biopharmaceutics: Topical Delivery of Keloid Therapeutic Drug,Tranilast, by Combined Use of Oleic Acid and Propylene Glycol as a Penetration Enhancer: Evaluation by Skin Microdialysis in Rats

Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm²), the maximum concentration of tranilast in skin dialysate was approximately 2 μM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10–20 μM, and this value was further increased to 60 μM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC_0–4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC_0–4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3–5% of that applied in the ethanol solution containing oleic acid, and 14–16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.     

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.