Studies of structure-activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage

The protective effects of stable nitroxides, as well as their hydroxylamine and amine precursors, have been tested in Chinese hamster V79 cells subjected to H2O2 exposure at fixed concentration or exposure to ionizing radiation. Cytotoxicity was evaluated by monitoring the viability of the cells assessed by the clonogenic assay. The compounds tested at fixed concentration varied in terms of ring size, oxidation state, and ring substituents. Electrochemical studies were carried out to measure the redox midpoint potentials. The studies show that in the case of protection against H2O2 exposure, the protection was determined by the ring size, oxidation state, and redox midpoint potentials. In general the protection factors followed the order nitroxides > hydroxylamines > amines. Both the six-membered ring nitroxides and substituted five-membered ring nitroxides were efficient protectors. For six-membered ring nitroxides, the compounds exhibiting the lowest midpoint potentials exhibited maximal protection. In the case of X-radiation, nitroxides were the most protective though some hydroxylamines were also efficient. The amines were in some cases found to sensitize the toxicity of aerobic radiation exposure. The protection observed by the nitroxides was not dependent on the ring size. However, the ring substituents had significant influence on the protection. Compounds containing a basic side chain were found to provide enhanced protection. The results in this study suggest that these compounds are novel antioxidants which can provide cytoprotection in mammalian cells against diverse types of oxidative insult and identify structural determinants optimal for protection against individual types of damage.     

Cloning, characterization, and tissue expression pattern of mouse tuftelin cDNA

Tuftelin is a protein that has been suggested to function during enamel crystal nucleation. Published sequences for bovine tuftelin cDNA and genomic clones proposed different reading frames that radically affected the derived amino acid sequence of the tuftelin carboxyl-terminus. We have isolated and characterized a full-length mouse cDNA clone and a partial porcine cDNA clone that include the region of the proposed frame-shift. The mouse tuftelin clone is 2572 nucleotides in length, exclusive of the poly(A+) tail. Translation from the 5'-most ATG yields a protein of 390 amino acids with an isotope-averaged molecular mass of 44.6 kDa and an isoelectric point of 5.9. Comparison of the bovine, mouse, and porcine cDNAs supports the revised bovine tuftelin amino acid sequence and suggests that the bovine tuftelin translation initiation codon be re-assigned to a more 5' ATG. Re-assigning the translation initiation codon lengthens the tuftelin protein by 52 amino acids, 51 of which are identical between bovine and mouse. At the carboxyl-terminus, the revised bovine and the mouse sequences match at 39 of the final 42 amino acid positions, compared with 2 identities with the originally published bovine reading frame. Northern blot analysis reveals that tuftelin is not ameloblast-specific but is expressed in multiple tissues, including kidney, lung, liver, and testis. Two tuftelin RNA messages, of 2.6 and 3.2 kb, were detected. DNA sequence characterization of an RT-PCR amplification product confirmed expression of tuftelin in kidney, and identified an alternatively spliced mouse tuftelin mRNA lacking exon 2.     

Facile minimally invasive cardiac surgery via ministernotomy

BACKGROUND: The public's and surgeons' perception of minimally invasive operations are frequently at odds. Nevertheless, real or perceived benefits may result from limiting skin and skeletal trauma. METHODS: Beginning in January 1996, we began approaching most infant and pediatric open heart procedures through an upper sternal split incision using a 1- to 3-inch skin opening and then extended this technique using a 2.5- to 3.5-inch incision for adult aortic and mitral valve replacement. RESULTS: A total of 82 patients, 57 infants and children and 25 adults, have been operated on using this approach (age range, newborn to 81 years). Operations accomplished through ministernotomy have included aortic valvotomy, arterial switch, tetralogy of Fallot, atrial or ventricular septal defect closure, aortic valve replacement, mitral valve replacement and repair, redo aortic or mitral valve replacement, double valve replacement, aortic root replacement, and complex arch reconstruction. In adults, the sternum was divided and then a T incision was made at the second, third, or fourth intercostal space. The mitral valve was reached through the roof of the left atrium. In children, a lower sternal split was used for atrial septal defect repairs. All cannulas were introduced through the ministernotomy incision, eliminating femoral cannulation. No new instruments, retractors, or ports were used. Mediastinal drainage was accomplished through a Blake drain connected to Heimlich-valved grenade suction. All but 2 patients were extubated immediately. Hospital stay was from 1 to 20 days (median 2 days). Patient and family acceptance is very high. CONCLUSIONS: On the basis of this initial experience, we attempt all congenital cardiac and isolated adult valve operations through ministernotomy.     

Noninvasive detection of cerebral hypoperfusion and reversible ischemia from reductions in the magnetic resonance imaging relaxation time, T2

STUDY DESIGN: Consecutive case retrospective chart review. OBJECTIVES: First, to assess whether the number of' patients requiring a second cervical surgical intervention was changed as a result of using anterior cervical plate stabilization, and second, to determine the additional risks and/or benefits associated with the hardware implantation. SUMMARY OF BACKGROUND DATA: The optimal technique of performing stabilization, arthrodesis, and alignment of a cervical segment after discectomy with neural decompression in degenerative disease has yet to be determined. METHODS: The charts of 402 patients who had undergone an anterior cervical discectomy and arthrodesis for degenerative disease performed both with and without anterior cervical plate stabilization were reviewed, and reoperation data were compiled. The average follow-up time was 3.8 years (range, 1.5-9.4 years). RESULTS: Of 365 patients with 1- or 2-level cervical arthrodesis, 22 required a second surgical intervention (20 bone alone, 2 with anterior cervical plate stabilization). The Log-Rank test, which uses all patients and their total follow-up periods, was statistically significant favoring anterior cervical plate stabilization at one and two levels (P = 0.015). CONCLUSIONS: The addition of anterior cervical plate stabilization in one- and two-level cervical degenerative disease supplements the internal stabilization initially provided by the bone graft, and yields a lower reoperation rate.     

Informed consent for epidural analgesia in labor

Characteristics and reproducibility of bulbocavernosus reflex (BCR) and pudendal somatosensory evoked potentials (PSEP) elicited by mechanical stimulation in children were tested. Twenty-five male children aged 5-14 years without uroneurological complaints were enrolled in the study. In addition to electrical stimulation, a specially constructed electromechanical hammer triggered by an oscilloscope was used for mechanical stimulation of distal penis. All responses were detected by surface electrodes. The latencies and amplitudes of averaged as well as latencies of single BCR on single and double electrical stimuli were determined. Mechanical stimulation was described as much less unpleasant than electrical stimulation. Both mechanical/electrical stimulation elicited consistent and reproducible responses in high percentages of children (BCR: average, 80%/71%, single, 94%/100%; PSEP: 96%/96%, respectively). BCR latencies were significantly longer and PSEP amplitudes were significantly higher on mechanical stimulation. The compliance with mechanical was much better than with the electrical stimulation and the former can be recommended for clinical use. The effective mechanical stimulus delivered by a particular mechanical stimulator has a characteristic 'delay' (as to the actual point of triggering the oscilloscope ray) which influences the latency reading of responses; appropriate control data are therefore necessary.     

Clinical evaluation of the HeartPak. A new pneumatic portable driver for use with the HeartMate Implantable Pneumatic Left Ventricular Assist System

The HeartPak Portable Pneumatic Driver was designed for use with the HeartMate Implantable Pneumatic Left Ventricular Assist Device (IP-LVAS) (Thermo Cardiosystems, Inc., Woburn, MA). The HeartPak measures 48 x 23 x 15 cm, weighs 9.3 kg with batteries, and can be carried by a handle, by a shoulder strap, or on a trolley. Four 12 V batteries provide power for as long as 8 hr. To test the HeartPak in the hospital environment, seven men were studied who were bridge-to-transplant patients (mean age, 59.8 +/- 8.87 years) undergoing HeartMate IP-LVAS therapy. They were supported by the HeartPak for 429 days with a cycle count of 57,826,560. To normalize the mean pump flow rate, we used the body surface area to obtain a pump flow index in each case. The mean flow rate was 2.65 +/- 0.57 L/min/m2 for the HeartPak vs. 2.64 +/- 0.45 L/min/m2 for the HeartMate 1000, the conventional driver previously used in these patients. The only potentially serious problem with the HeartPak was console failure in one case. The patient took appropriate backup measures, and the HeartPak was replaced. In no case did the device cause any adverse effects or interruption of LVAS support. Compared with HeartMate 1000, the HeartPak was more convenient, easier to operate, and allowed better patient mobility.