Surgical repair of type A aortic dissection by the circulatory arrest-graft inclusion technique in sixty-six patients

During an 8-year period (1984 to 1991) 66 patients (mean age 59 years, range 26 to 84 years) with type A aortic dissection (60 ascending aorta tears, 6 arch tears; 35 acute, 31 chronic) had surgical repair by a continuous suture-graft inclusion technique. Hypothermic circulatory arrest (16 degrees C) was used in 58 patients (35/35 acute, 23/31 chronic; mean arrest time 26 minutes, range 10 to 55 minutes). Fifty-two patients had hemiarch repair and 6 had total arch replacement. Aortic valve disease necessitated treatment in 38 patients (1 valved conduit, 20 valve replacements, 17 valve repairs). Recently 11 patients had valve repair by reconstruction of the native aortic root, by means of techniques similar to those used for homograft valve insertion. Operative mortality was 9% (14% acute, 3% chronic). Stroke occurred in 2 patients (3%) and was fatal in both. Variables suggestive of increased operative risk by univariate analysis were acuteness (p = 0.12), visceral ischemia (p = 0.12), and preoperative shock (p = 0.13). No variable was significant by multivariate analysis. Overall actuarial survival at 48 months was 77%, with 3 late deaths from a ruptured distal aneurysm. Late computed tomography or magnetic resonance imaging scan was done in 28 patients at a mean interval of 33 months. These studies identified 1 patient with a pseudoaneurysm requiring reoperation and 3 patients with contained flow between the graft and the wrap. Three patients required late operation: 1 for pseudoaneurysm, 1 for arch dissection, and 1 for repair of a distal aneurysm.     

Aldehyde disinfectants and health in endoscopy units. British Society of Gastroenterology Endoscopy Committee

Summary of main recommendations(1) Glutaraldehyde, used in most endoscopy units in the United Kingdom for the disinfection of flexible gastrointestinal endoscopes, is a toxic substance being an irritant and a sensitiser; symptoms associated with glutaraldehyde exposure are common among staff working in endoscopy units.(2) The Control of Substances Hazardous to Health Regulations 1988 (COSHH) obliges the employer to make a systematic assessment of risk to staff of exposure to glutaraldehyde and institute measures to deal effectively with exposure.(3) At present glutaraldehyde remains the first line agent for the disinfection of flexible gastrointestinal endoscopes. Other agents are being developed; a standard means of assessment for flexible endoscope disinfectants should be devised.(4) Equipment and accessories that are heat stable should be sterilised by autoclaving; disposable accessories should be used wherever possible.(5) Flexible gastrointestinal endoscopes should be disinfected within automated washer/disinfectors; trays, bowls or buckets for this purpose are unacceptable.(6) Local exhaust ventilation must be used to control glutaraldehyde vapour. Extracted air may be discharged direct to the atmosphere or passed over special absorbent filters and recirculated. Such control measures must be regularly tested and records retained.(7) Endoscope cleaning and disinfection should be carried out in a room dedicated to the purpose, equipped with control measures to maintain the concentration of glutaraldehyde vapour at a level certainly below the current occupational exposure standard of 0.2 ppm and preferably below the commonly used working limit of 0.1 ppm. Sites other than the endoscopy unit where endoscopy is regularly performed, such as the radiology department, should have their own fully equipped cleaning and disinfection room.(8) COSHH limits the use of personal protective equipment to those situations where other measures cannot adequately control exposure. Such equipment includes nitrile rubber gloves, apron, chemical grade eye protection, and respiratory protective equipment for organic vapours.(9) Monitoring of atmospheric levels of glutaraldehyde should be performed by a competent person such as an occupational hygienist; the currently preferred method of sampling uses a filtration technique, the commercially available meters being less reliable.(10) Health surveillance of staff is mandatory; occupational health records must be retained for 30 years.(11) Endoscopy staff must be informed of the risks of exposure to glutaraldehyde and trained in safe methods of its control. Only staff who have completed such an education and training programme should be allowed to disinfect endoscopes.(12) The unsafe use of glutaraldehyde has significant health and legal consequences; the safe use of glutaraldehyde may have revenue consequences that contribute significantly to the cost of gastrointestinal endoscopy.     

Cardiomyoplasty: hemodynamic benefit to normal and depressed canine left ventricular function

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.     

Activation of the cloned human NK3 receptor in Chinese Hamster Ovary cells characterized by the cellular acidification response using the Cytosensor microphysiometer

1. The aim of the present study was to validate the Cytosensor microphysiometer, a novel system that measures the extracellular acidification rate as a reliable index of the integrated functional response to receptor activation, as a method for studying NK3 receptor pharmacology, and then to use this system to assess the functional activity of novel compounds at this receptor. 2. The selective NK3 agonist senktide caused reproducible, concentration-related increases in acidification ratein CHO-NK3 cells, with a pEC50 value of 8.72+/-0.11 (n=15). [Beta-Ala8]NKA(4-10), the selective NK2 agonist, elicited a much weaker response (pEC50=6.68+/-0.08, n=4), while the NK1-selective agonist substance P methylester only caused a very weak response at concentrations > or =3 microM (n=2). The rank order of potency for the endogenous tachykinins NKB>NKA>substance P (n=3) confirmed the response was mediated by the NK3 receptor. Moreover, the actual potencies obtained were consistent with affinities measured in radioligand binding studies. 3. The novel compounds PD156319-121 (0.3-1 microM), PD161182 (10-300 nM), PD168001 (10-100 nM) and PD168073 (10-100 nM) all acted as surmountable antagonists of the senktide-induced acidification response, with pA2 values of 7.49, 8.67, 9.17 and 9.25 respectively (n=3-5). In comparison the known NK3 antagonist SR142801 (10-100 nM) had a pA2 value of 8.83 (n=8) for the interaction with senktide. Again, these values are consistent with the radioligand binding data. 4. Amiloride (1 mM) inhibited the senktide-induced acidification response by 68.3+/-3.3 (n=4), indicating that the Na+/H+ antiporter plays an important role in this response, and this is consistent with the importance of this antiporter in other acidification responses. 5. Inhibition of protein kinase C with staurosporine (0.1 microM), or depletion of the intracellular Ca2+ stores with thapsigargin (1 microM), both resulted in a reduction in the maximum response to senktide (63.3+/-1.7 and 68.9+/-3.2% respectively, n=3-5), and co-application of these inhibitors abolished the response (n=3). This strongly suggested that the NK3 receptor was coupling via phospholipase C (PLC), as would be expected, although this could not be confirmed by the use of the putative PLC/PLA2 inhibitor U73122. 6. In conclusion, we have demonstrated the utility of the Cytosensor in the characterization of functional responses to agonists, and assessment of the affinities of antagonists in CHO cells expressing the human NK3, and have shown that our series of novel compounds are non-peptide NK3 antagonists of high affinity, as exemplified by PD168073.     

Antioxidant activity, packed cell transfusions, and outcome in premature infants

AIM: To evaluate the relative importance of biochemical markers of antioxidant status, gestational age, and parameters of neonatal care in the clinical outcome of premature infants. METHOD: A prospective, observational, longitudinal study of the association between these factors was conducted. Blood was collected from an in situ arterial line within two hours of birth and at intervals thereafter, when blood was drawn for routine clinical purposes. Outcome was assessed as death, or survival with or without bronchopulmonary dysplasia (BPD). One hundred and forty four babies of 22 to 39 weeks of gestation, who required intensive care at the Jessop Hospital for Women, between January 1993 and April 1994, were recruited. RESULTS: Low gestational age at birth was the most important predictor of mortality and the development of BPD. Having corrected for gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Plasma vitamin C at birth was significantly higher in the babies who died compared with those with a good outcome, but this effect was not sustained after correcting for gestational age. Repeated measures of Analysis of Variance revealed a postnatal increase in antioxidant activity, caeruloplasmin, retinol, cholesterol corrected alpha tocopherol, and red blood cell superoxide dismutase (SOD) activity. Vitamin C, on the other hand, declined in all groups after birth. Logistic regression analysis revealed that the greater the number of packed cell transfusions received during intensive care, and the higher the concentration of vitamin C on the second day of life, the greater the risk of developing BPD. CONCLUSIONS: After correcting for the effect of gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Frequent blood cell transfusions over the first week of life are associated with an increased risk of developing BPD. This association may be causal.     

The present state of the art in chemotherapy for soft tissue sarcomas in adults: the EORTC point of view

In the present study effects of light on the sleep duration of anesthetized hornets (Vespa orientalis) were investigated. Following initial anesthesia by diethyl ether the sleeping time of workers and drones at 22 degrees C in the dark was 59 +/- 15 min. After repeated anesthesia the sleeping time was 30 +/- 15 min in the dark. When exposed to polychromatic light from a halogen lamp of 230 mW/cm2, focused on a spot of the cuticle of the hornet, the sleeping time was markedly shortened so that following initial as well as repeated anesthesia the hornets woke up after 4.5 +/- 2.9 min. Any decrease in light intensity resulted in an increase in the sleeping time but irradiances of less than 14 mW/cm2 had no measurable influence on the wake-up time. After illumination with polychromatic light from a mercury lamp the sleeping times were much shorter than after illumination with a halogen lamp at the same conditions and intensity. This difference is attributed to the relatively higher portion of U.V. light in the total emission of the Hg lamp. Effects of the spectral composition of the incident light beam on the wake-up of the sleeping hornets were also investigated. Near U.V. light in the 300-400 nm region was found to be most efficient. Shorter wavelengths as well as wavelengths between 400-470 nm had less influence and wavelengths above 470 nm had very little effect on the wake up. The sleeping times of hibernating queens were relatively longer than those of workers and drones under the same conditions. These effects are ascribed to the extraretinal light perception. The possible reasons underlying this phenomenon are discussed.     

A high-resolution metric HAPPY map of human chromosome 14

We have mapped 1001 novel sequence-tagged sites on human chromosome 14. The mean spacing between markers is approximately 90 kb, most markers are mapped with a resolution of better than 100 kb, and physical distances are determined. The map was produced using HAPPY mapping, a simple and widely applicable in vitro approach that is analogous to linkage or to radiation hybrid mapping, but that circumvents many of the difficulties and potential artifacts associated with these methods. We show also that the map serves as a robust scaffold for building physical maps using large-insert clones.