Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat

The isolated perfused working rat heart model of cardiopulmonary bypass was used to assess whether (a) allopurinol pretreatment enhances resistance to normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to cardioplegic and/or reperfusion solutions are protective; (c) any protective effects are additive. With normothermic ischemia, allopurinol pretreatment improved recovery of aortic flow from its control value of 25 +/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during both ischemia and reperfusion improved recovery of aortic flow from a control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However, various combinations of the two types of intervention afforded no additive protection. Under hypothermic (21 degrees C) conditions, allopurinol pretreatment was not effective, whereas SOD and CAT added during ischemia and reperfusion improved recovery of aortic flow from its control value of 53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to allopurinol pretreatment and SOD plus CAT added during ischemia and reperfusion (69 +/- 6%: P less than 0.05). These results provide further evidence that reperfusion-induced free radical formation may adversely affect postischemic recovery of function. The absence of an additive effect suggests a common mechanism of action, which is likely to involve the free radical-generating enzyme xanthine oxidase; however, other mechanisms may exist. Our results further support the use of antifree radical intervention in conjunction with cardioplegia to protect the heart during ischemia and reperfusion.     

Injection of botulinum A toxin into the gastrocnemius muscle of patients with cerebral palsy: a 3-dimensional motion analysis study

Botulinum A toxin (BOTOX^®) was injected into the gastrocnemius muscle of 26 cerebral palsy subjects with equinus gait. All subjects were equinus walkers without fixed contracture of the triceps-surae muscle. Injections were performed at 3 month intervals, if needed, as determined by the treating clinician. There were 14 subjects with spastic hemiplegia, 11 subjects with spastic diplegia and 1 subject with spastic quadriplegia. In the case of those subjects with bilateral equinus gait the dose was divided and given into both the right and left gastrocnemius muscle. Gait analysis data was collected prior to the first injection and subsequently at 3 month intervals for 1 year. Kinematic and electromyographic data was obtained. This data was analyzed to provide objective information about the outcome of treatment. Four subjects moved away and were lost to follow-up. Seven subjects left the study to have surgery. The data collected revealed statistically significant improvements in dynamic ankle dorsiflexion in both stance and swing phases, stride length, and electromyography of the tibialis anterior. There were no complications. While the results of this study are promising, additional prospective studies are needed to determine the feasibility of preventing muscle contractures over a longer time period. Furthermore, there is a need for inclusion of other muscles in future research. Future research should also compare BOTOX^® treatment with alternative methods of dealing with muscle spasticity such as: casting, orthotic devices, physical therapy, selective dorsal rhizotomy, and surgical lengthening.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

Recruiting for success--the potential for using occupational personality questionnaires for the assessment of doctors.

OBJECTIVES: to evaluate the Saville and Holdsworth Occupational Personality Questionnaire (OPQ) to assess its potential and validity as a tool in the recruitment of doctors. To determine the range of personality characteristics in a group of general practitioners. DESIGN: an administered commercially available questionnaire. SETTING: general practitioners in North and Mid. Stafftordshire. SUBJECTS: 133 general practitioners or trainees. RESULTS: 44% of general practitioners agreed to participate. The majority found it useful and recognised its potential to increase self-awareness, highlight weaknesses that might be improved and for future recruitment of others to their teams. Doctors' personality traits were similar to those of managerial/professional norms. The validity of the OPQ was supported by (a) significant associations with subjects' previously reported mental health problems and (b) 83% of respondents confirming that their reports correctly described their personalities at work. CONCLUSIONS: OPQs have a place in the recruitment of doctors by identifying appropriate people to strengthen the team.     

The amplitude modulation-following response as an audiometric tool.

The amplitude modulation-following response (AMFR) is an auditory scalp-recorded potential, evoked using continuous, amplitude-modulated tones. The current study was designed to explore the audiometric utility of the AMFR by demonstrating the frequency specificity of the response and assessing the relation between behaviorally measured pure-tone thresholds and AMFR detection thresholds. Subjects in this study were six normal-hearing and four hearing-impaired adults. High-pass masking results in the normal hearing subjects demonstrated that the AMFR is associated with a narrow range of activation along the cochlea around the carrier frequency. Frequency-specific results from the hearing-impaired subjects confirmed this finding. Thresholds for the AMFR, defined in spectral terms, were consistent with the behavioral estimates in both the normal and the hearing-impaired subjects.     

Do symptoms reflect a change in left ventricular function after aortocoronary bypass grafting in patients with depressed left ventricular function?

Seventy-nine patients with moderate to severe left ventricular dysfunction who underwent aortocoronary bypass grafting between 1971 and 1977 had follow-up heart catheterization at a mean interval of 3 years. Thirty-three patients (42%) had angiographic improvement in left ventricular function at follow-up and 18 (25%) had a decrease in left ventricular end-diastolic pressure. Fifty-eight patients (73%) had improvement in angina of at least one New York Heart Association class at follow-up. There was no correlation between late improvement in left ventricular function and improvement in angina. Improvement in left ventricular function did not correlate with preoperative indices of severity of coronary disease or with indices of completeness of surgical repair.