Unilateral high frequency jet ventilation. Reduction of leak in bronchopleural fistula.

A young alcoholic presented with severe bilateral bronchopneumonia, which required prolonged treatment with intermittent positive pressure ventilation. High airway pressures were necessary for effective gas exchange. A recurrent tension pneumothorax led to a persistent bronchopleural fistula which resulted in hypercarbia and hypoxaemia despite the use of large minute volumes. Surgical resection was not considered feasible because of extensive local infection. Asynchronous independent lung ventilation was instituted, using a double-lumen endobronchial tube. A considerable leak still occurred through the bronchopleural fistula, and it was only when high frequency jet ventilation was substituted to the fistula-containing lung that the leak was virtually abolished, while improving gas exchange. High frequency jet ventilation in bronchopleural fistula is of potential benefit.

Effects of spaceflight on morphology of the rat adenohypophysis.

To determine the effects of spaceflight on the anterior pituitary gland, the adenohypophyses of rats after a 7-day spaceflight aboard the space shuttle Endeavor (STS-54) were investigated by histology, immunohistochemistry, morphometry, electron microscopy, and in situ hybridization and were compared with synchronous control rats. Morphometry revealed the corticotrophs of space-flown rats to be significantly enlarged, demonstrating 46-48% increases in mean cell, nuclear, and cytoplasmic areas. These corticotrophs also exhibited striking ultrastructural signs of heightened secretory activity. Furthermore, their expression of proopiomelanocortin mRNA, the transcript encoding the precursor protein from which adrenocorticotropic hormone is posttranslationally cleaved, was also significantly enhanced, a finding consistent with their hypersecretory state. Gonadotrophs also exhibited significant increments in mean nuclear, cell, and cytoplasmic areas of 22, 45, and 51%, respectively; however, they were not accompanied by ultrastructural evidence of increased secretory function. There were no morphological changes in somatotrophs, lactotrophs, or thyrotrophs, nor were there any significant changes in the overall frequency of any one adenohypophyseal cell type in comparison with control. The structural integrity of all adenohypophyseal secretory and vascular elements was preserved after spaceflight, as there was neither evidence of necrosis nor other forms of cellular injury in spaceflown specimens. Capillaries were patent, and neither endothelial damage nor thrombosis was noted. These data suggest that spaceflight is accompanied by a selective morphological response in the anterior pituitary, one characterized by hypertrophy of both corticotrophs and gonadotrophs and by enhanced endocrine activity of the former.

Clinical evaluation of an inexpensive ultrasound oculometer for ocular biometry.

We measured anterior chamber depth and axial length in 200 human eyes with the Echo-Oculometer and the Digital Biometric Ruler. There was good agreement between measurements with the two instruments. The echo-Oculometer is much less expensive than any other instrument available for measuring ocular axial length and satisfactorily provides information for calculation of power of intraocular lenses.

The significance of membrane changes in the safe and effective use of therapeutic and diagnostic ultrasound.

The cellular changes, such as alterations in motility and the stimulation of synthesis and secretion, induced by relatively low intensities of therapeutic ultrasound (e.g. 500 mW cm-2, SAPA; 100 mW cm-2 SATA) are primarily non-thermal in origin. They appear to be associated with changes in the permeability of the cell (plasma) membrane and in the transport of ions and molecules across it, effects which have been demonstrated in cells irradiated in suspension. In epithelial tissues, both in vitro and in vivo, it has been demonstrated that not only the cellular membrane transport pathways but also the paracellular or intercellular pathways are affected. Although membrane-mediated effects can be of value therapeutically, they could produce adverse effects if they were to occur during development, for the reception and transmission by the membrane of environmental signals are involved in determination of the fate of each cell. Determination is followed by selective gene expression and differentiation, that is, by the progressive increase in structural complexity brought about by the acquisition of specialised characteristics by various cell groups. Most cells of early embryos are ionically coupled via gap junctions which provide an intercellular pathway for electrochemical signalling and the maintenance of the concentration gradients which provide the cells with positional information. Differentiation of the cells varies according to their location with respect to these gradients. Increase in the intracellular concentration of calcium ions, which has been shown to occur after exposure to therapeutic levels of ultrasound, can decrease the permeability of gap junctions and uncouple cells, in the manner which occurs when they differentiate. Ultrasonically induced increases in calcium ion concentration are thus of considerable clinical significance, since they could affect differentiation and consequently histogenesis. Modification of plasma membrane permeability and transport properties, resulting in changes in the availability and activity of second messengers such as free calcium ions, can have profound effects on cell behaviour. Calcium channels appear to be the first channels to develop in the cell membranes of embryos, and internal calcium ion concentration is known to affect the synthesis of fetal proteins. Although generally reversible at intensities of less than 500 mW cm-2, changes in membrane permeability, particularly to calcium ions, could, if prolonged, have undesirable side effects not only on embryogenesis but on late prenatal and postnatal development. It is therefore recommended that the environmental conditions, thresholds, and mechanisms involved in the production of such changes be determined, so that they can be avoided when ultrasound is used diagnostically on sensitive targets such as embryos and fetuses.

The effect of therapeutic ultrasound on calcium uptake in fibroblasts.

The effect of therapeutic ultrasound on calcium uptake by embryonic chick 3T3 fibroblasts has been studied using calcium-45 radiotracer techniques. Cells were treated while suspended in culture medium at 36 degrees C at intensities from 0.25 W/cm2 SPPA to 1.5 W/cm2 SPPA (1 MHz, pulsed 2 ms on:8 ms off) and for exposure times from 1 min to 20 min. Ultrasound treatment was found to increase calcium uptake for SPPA intensities from 0.5 to 1.0 W/cm2 SPPA, with a maximum increase of 18% after a 5 min exposure. Calcium uptake also increased with increasing exposure time. Measurements performed up to 20 min after treatment showed that the cell was able to reduce this calcium influx, indicating that the membrane did not suffer irreparable damage as a result of the ultrasound exposure.

A cavitation and free radical dosimeter for ultrasound.

A simple and sensitive method is described for measuring the number of hydroxyl radicals (.OH) produced in aqueous solution by high intensity ultrasound (US). The method is based on the conversion of nonfluorescent terephthalic acid (TA) to highly fluorescent hydroxyterephthalate (HTA). The spectrofluorimeter is calibrated by use of a TA solution which has been exposed to a reference dose of cobalt-60. This allows fluorescence readings produced by ultrasound to be read directly in equivalent centiGrays (cGy). The limit of detection for OH is about 1.3 X 10(-9) M (equivalent to an exposure of about 0.5 cGy of cobalt-60). The threshold for transient cavitation (TC) in an air-saturated aqueous solution was found at 0.7 watts per cm2. Cavitation was consistently produced when TA was exposed in a soft vinyl chamber and only when the chamber was being rotated about an axis which was perpendicular to the US beam. The use of TA as a quantitative indicator of transient cavitation should be of value to the study of ultrasonic biological effects and dosimetry.

Ultrasound intensity and contractile characteristics of rat isolated papillary muscle.

The effect of graded intensities of continuous wave ultrasound on the contractile performance of isolated papillary muscle of rat was tested. Under isometric conditions rat left ventricular papillary muscles (n = 48) were electrically stimulated to contract at rates of 30, 60, 120 and 240 beats per minute. Muscles were perfused with a Tyrode solution at 30 degrees C under normoxic conditions. Ultrasound at intensities of 0.25, 0.50, 1.0 and 2.0 W/cm2 spatial average temporal average (SATA) at 963 kHz was applied to the muscles while recording muscle contractile characteristics. The analog data were digitized and stored on disk for analysis by computer. This revealed a significant (p less than 0.001) increase in peak developed force (F), peak rate of force development (+dF/dt) and peak rate of myocardial relaxation (-dF/dt) that was linearly related to ultrasound intensity. The muscles were more sensitive to ultrasound at 240 contractions per minute. Resting force was significantly decreased by ultrasound. Although bath temperature increased according to the ultrasound intensity, control studies in papillary muscles (n = 24) on the correlation between contractile parameters and temperature revealed that bulk heating could not account for the positive inotropic action with ultrasound. These data confirm the inotropic effect of continuous wave ultrasound on myocardial tissue and point to the possibility of applying this phenomenon therapeutically.

Educational projects in Space Life Sciences in Canada.

As part of its mandate the Space Life Sciences Program within the Canadian Space Agency has worked to increase interest in space and develop young scientists. Projects have been undertaken at the public school and high school level, with classroom resource material and science contests; at the university level with summer training programs, and at the post-graduate level with opportunities to complete research projects in a microgravity environment.

Ultrasound-enhanced diffusion through isolated frog skin.

The effect of ultrasound on the transport of oxygen across excised frog abdominal skin has been studied. Samples were mounted in an exposure chamber in which the Ringer's solution on one side was saturated with oxygen while the other side of the skin had a low initial oxygen concentration. They were treated with ultrasound at 1, 1.5 and 2 W cm-2 SATA c.w., respectively, and increases in the rate of oxygen transport were observed at all intensities. These increases ranged from 38 +/- 4% at 1 W cm-2 to 55 +/- 8% at 2 W cm-2. Variation in the pulse lengths from 25 to 200 ms and a constant average intensity did not affect the rate of transport significantly provided that the temporal intensity was constant. Since the peak acoustic pressure within the pulse increased with decreasing pulse length and increasing acoustic pressure increases the probability of cavitation occurring, the mechanism responsible for this phenomenon is probably not cavitation.

The effects of ultrasound on the mechanical properties of rat cardiac muscle.

The mechanical properties of cardiac muscle during ultrasonic irradiation have been studied in vitro. Left anterior papillary muscle from normal rats was suspended in buffered lactated Ringers solution equilibrated with 95% O2, and 5% CO2 and maintained at 20 degrees C. The muscles were stimulated to contract isometrically three times per minute at the length which produced maximum tension. Each muscle was irradiated with a MHz ultrasound at an average power of 2.4 Wcm-2 for a period of 10 min with a 10 min recovery period. Irradiation caused an average increase in temperature of the muscle of 1.7 +/- 0.2 degrees C (mean +/- SEM). Irradiation caused the resting tension (1.46 +/- 0.13g) to decrease by 17.8 +/- 4.7% and the developed tension (3.33 +/- 0.61g) to decrease by 4.1 +/- 0.9%. Since changes in contractile properties have been reported with temperature the bath temperature was raised and changes in contraction observed. When compensated for effects of temperature, the changes in resting tension became - 13.3 +/- 4.1% while the change in developed tension became + 1.6 +/- 2.3%. The change in resting tension is highly significant (p less than 0.05 paired t-test) while the change in developed tension is not. Thus 1 MHz ultrasound at an intensity of 2.4 Wcm-2 appears to affect resting tension of cardiac muscle without affecting the active tension. Since changes in cardiac mechanics of this type have not been described previously the effects of ultrasound appears to be unique.

Life science research in space brings health on Earth.

NASA: Leading scientists and physicians review groundbreaking research that is leading the way to better health care for astronauts and new treatments for medical problems on Earth. This research includes the development and testing of a new Ventricular Assist Device for patients with heart failure awaiting heart transplantation; advancements in telemedicine that bring medical care to remote areas on Earth and aid in the diagnosis and treatment of illness during space flight; advanced technologies, such as a miniature mass spectrometer, cardiac ultrasound equipment, bone imaging, non-invasive High-Intensity Focused Ultrasound, non-invasive techniques for blood and tissue chemistry measurements; and advances in the treatment of spinal cord injuries.^ieng

National comparative audit of blood use in elective primary unilateral total hip replacement surgery in the UK.

INTRODUCTION: Blood is a scarce and expensive product. Although it may be life-saving, in recent years there has been an increased emphasis on the potential hazards of transfusion as well as evidence supporting the use of lower transfusion thresholds. Orthopaedic surgery accounts for some 10% of transfused red blood cells and evidence suggests that there is considerable variation in transfusion practice. PATIENTS AND METHODS: NHS Blood and Transplant, in collaboration with the Royal College of Physicians, undertook a national audit on transfusion practice. Each hospital was asked to provide information relating to 40 consecutive patients undergoing elective, primary unilateral total hip replacement surgery. The results were compared to indicators and standards. RESULTS: Information was analysed relating to 7465 operations performed in 223 hospitals. Almost all hospitals had a system for referring abnormal pre-operative blood results to a doctor and 73% performed a group-and-save rather than a cross-match before surgery. Of hospitals, 47% had a transfusion policy. In 73%, the policy recommended a transfusion threshold at a haemoglobin concentration of 8 g/dl or less. There was a wide variation in transfusion rate among hospitals. Of patients, 15% had a haemoglobin concentration less than 12 g/dl recorded in the 28 days before surgery and 57% of these patients were transfused compared to 20% with higher pre-operative values. Of those who were transfused, 7% were given a single unit and 67% two units. Of patients transfused two or more units during days 1-14 after surgery, 65% had a post transfusion haemoglobin concentration of 10 g/dl or more. CONCLUSIONS: Pre-operative anaemia, lack of availability of transfusion protocols and use of different thresholds for transfusion may have contributed to the wide variation in transfusion rate. Effective measures to identify and correct pre-operative anaemia may decrease the need for transfusion. A consistent, evidence-based, transfusion threshold should be used and transfusion of more than one unit should only be given if essential to maintain haemoglobin concentrations above this threshold.

Routine pre-operative blood testing: is it necessary?

In order to determine the value of routine pre-operative screening investigations, the medical notes of 100 patients undergoing elective surgical procedures under general anaesthesia were subject to prospective audit. Pre-operative screening investigations (full blood count, urea and electrolytes and random glucose) were analysed in terms of frequency of abnormalities and whether or not the peri-operative management was changed when the result was abnormal. The frequency of results being present in the note at the time of operation and the costing of the tests was also examined. A total of 773 tests was performed of which 70 (9.1%) were abnormal. Peri-operative management was altered as a result of only two abnormal results (0.2%). Eight complications arose, none of which could have been predicted by the pre-operative screening tests. In only 57% of cases were the results present in the medical notes at the time of surgery. It is conservatively estimated that a saving of pound 50 000 per year could be made in our hospital alone by selective ordering of tests.

Estimation of arterial PCO2 during high frequency jet ventilation. Studies in the dog.

The arterial to end-tidal PCO2 difference (PaCO2-PE'CO2) was measured in five anaesthetized dogs during controlled ventilation at 0.25 Hz (15 b.p.m.) and during high frequency jet ventilation at 1, 3 and 5 Hz. Because of the slow response of the infra-red carbon dioxide analyser, satisfactory recordings of end-tidal carbon dioxide could not be obtained at frequencies greater than 1 Hz. The interruption of high frequency jet ventilation by conventional ventilation resulted in approximately equal arterial and end-tidal PCO2 values during the first breath, and restoration of the normal arterial to end-tidal PCO2 difference by the third breath. It is concluded that, when high frequency jet ventilation at 1, 3 or 5 Hz is interrupted with normal tidal volumes at low frequencies, the arterial PCO2 can be estimated from recordings of the end-tidal PCO2.