Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery

Background: Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves.

Methods: Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used.

Results: Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated;P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J;P = 0.003), less cumulative energy (12.6 vs. 23.4 J;P = 0.002), and fewer shocks (2.5 vs. 3.5;P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested.     

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.     

Education of the aged in a residential setting--motivation for participation of "educational novices" within the scope of a "bring" structure

Every inhabitant aged 60 years and over in a working class district in Kassel (N = 568) was visited and invited to discussion groups (topics were "growing old", "health", "care" and others) and to excursion activities. 10% of the people were interested; 7% actually took part. In comparison with a control group of participants from other districts, it was shown that it is possible to mobilize some of those people who have had low-level schooling and only a little experience of further education.     

CGP 6809 — A new nitrosoureido-sugar derivative with activity in human tumor xenografts

Summary CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)--d-glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats [14]. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s. c. in nude mice. The p. o. administration of 125 mg/kg per day for 10–15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i. p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissure sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.Supported in part by grant PTB 8467 from the Bundesminister für Forschung und Technologie, Bonn, FRG     

Expression of human immunodeficiency virus type 1gag gene using genetically engineered herpes simplex virus type 1 recombinants

Infectious herpes simplex virus type 1 (HSV-1) recombinants were constructed by inserting the cDNA sequence of the human immunodeficiency virus type 1 (HIV-1)gag gene (from nucleotide position 675 [SacI] to 3859 [Asp 718] of the cDNA sequences of HIV-1 strain BH-10) within the DNA sequences of theBamHI DNA fragment B of the genome of an apathogenic HSV-1 strain HFEM. This HSV-1 strain possesses a 4.1-kbp deletion within theBamHI DNA fragment B between 0.762 and 0.789 map units of the viral genome, which allows the insertion of at least 4 kbp of foreign genetic material into this particular region. The DNA sequences of the immediate early promoter (IE4) of HSV-1 that were inserted upstream from thegag gene were used as a promoter. The screening of 205 virus stocks derived from individual plaques revealed that 46 recombinant viruses harbor HIV-1gag-specific DNA sequences. However, it was found that only six of the recombinant viruses are able to express thegag gene product of HIV-1. This indicates that the ratio of the positive recombination events is about 2.9%.     

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia

The brain serotonin-2A receptor (5-HT_2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT_2AR status before the onset of schizophrenia and before the exposure to antipsychotics. We used [¹⁸F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT_2AR binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT_2AR availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.     

Conductance properties and voltage dependence of an anion channel in amphibian skeletal muscle

Single anion-selective channels were studied in excised membrane patches of adult frog toe muscle. The conductance and the probabilityp _o of the main open state were determined for various ionic compositions of the extra-and intracellular solutions. =280 pS in symmetrical 110 mM NaCl, pH 7.4 solutions at 15°C. Higher values were found at elevated internal or external NaCl concentrations, in 70 mM external CaCl₂ and at lower extracellular pH. Thep _o(E) curve declined steeply with hyperpolarization and was shifted towards more negative potentials at increased internal ionic strength and at higher external pH. Positive shifts were induced by extracellular Ca. The results show that the anion channel saturates at Cl concentrations >110 mM, that the potential profile of an open channel is almost symmetrical and that channel gating is affected by neighboring channels. It is suggested that the anion channel has a voltage sensor (effective gating charge 4.3) and a similar collection of local fixed charges on the extra- and intracellular sides as voltage-gated cation channels.     

Low dose exposure to sodium arsenite synergistically interacts with UV radiation to induce mutations and alter DNA repair in human cells

Inorganic arsenic is a known human carcinogen, yet its mechanism of action remains poorly understood. Epidemiological data suggest that arsenic exposure interacts with UV radiation exposure to increase the risk of skin cancer. Studies have suggested that arsenic is able to impair DNA repair enzymes and alter the repair of UV-induced DNA damage. Here we have tested the hypothesis that arsenite [As(III)] and UV interact synergistically to enhance mutagenesis. TK6 human lymphoblastoid cells that are functionally heterozygous at the thymidine kinase (TK) locus were pre-exposed to As(III) alone and in combination with UV. Our data suggest that As(III) is mutagenic only at high doses at the TK locus. As(III) enhanced UV mutagenesis in a more than additive fashion. To investigate the mechanism underlying this synergy we assessed the removal of UV-induced dimers in TK6 cells using the T4 endonuclease-incorporated Comet assay. Pre-treatment with As(III) specifically inhibited the repair of UV-induced pyrimidine dimer-related DNA damage. Taken together, these data suggest that pre-treatment of human cells with arsenic impairs the nucleotide excision repair pathway and leads to enhanced UV mutagenesis.